MDedge Neurology

A sense of safety and stability, both emotional and physical, is crucial in promoting the healthy development of youth. Between the global pandemic, need for social distancing, economic downturn, and increased awareness of racial disparities, for many this sense of stability has been rattled.

Ryan McVay/ThinkStock

School closures have led to a loss of social interaction, challenges to continued academic growth, and, for some students, lack of access to nutrition and increased food insecurity. For students with learning or mental health challenges, closures may have eliminated or significantly reduced desperately needed supports received in school.¹ While these trying circumstances have been difficult for many, the transition back to school in the fall also may be challenging because of the uncertainty about what this will look like and possible change in routine. Some students or their families may have anxiety about returning, either because of a history of adverse experiences at school such as bullying, or because of fears about exposure for themselves or others to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The past several months also brought about greater awareness of systemic racial disparities, whether as reflected in health care, education, or the criminal justice system. According to the Centers for Disease Control and Prevention data, Latinx and African-American individuals in the United States have had a threefold greater chance of contracting SARS-CoV-2 and have a twofold greater risk of death, compared with white people in the same communities.² Other social determinants of health – economic stability, education, social factors such as incarceration and discrimination, and neighborhood factors including access to healthy food – play a role in this vulnerability.

The pandemic has resulted in a need for social distancing, and as a result, isolation. Children and teens exposed to the news may have anxiety about what they see or hear. Additional pressures in the family can include economic uncertainty, loss of employment for the primary wage earner of the household, or stress related to family members being first responders.

Any one of these factors is a potentially significant stressor, so how do we best support youth to help them survive and hopefully thrive during this time?
 

• It is important to establish a sense of routine; this can help create a sense of stability and safety. Recognizing that circumstances are not the same as they were 5 or 6 months ago, encouraging structure should not come at the cost of preserving connection.
• Note positive behavior and choices made by children and make sure they know it was observed.
• Many children have experienced increased screen time with the lack of structure of the traditional school day or summer camp and extracurricular activities. Limiting screen time and being mindful of its potential impact on mood is prudent.
• Self-care for parents and guardians is important. This is clearly a marathon and not a sprint; parents’ caring for themselves will place them in a better position to support their children. This time is stressful for the adults of the household, let alone children who are learning self-regulation skills.
• Listen to children’s or teens’ concerns and share information in developmentally appropriate ways. It is okay to not have all of the answers.
• Balance fostering a sense of gratitude with not invalidating a child’s or teen’s experience. Showing empathy during this time is vital. While there may be other soccer seasons, it is normal to experience grief about the loss of experiences during this time.
• Parents and guardians know their children best, so it is prudent for them to be mindful of concerning changes such as an increase in sadness, anxiety, or irritability that negatively impacts daily functioning such as sleeping, eating, or relationships with family and friends.
• Promote social interactions with appropriate safeguards in place. Unfortunately, the number of SARS-CoV-2 infections is increasing in multiple states, and there is the potential to return to some of the previous restrictions. However, encouraging social interaction while following local guidelines and with cautions such as limiting the number of people present, meeting outside, or considering interacting with others who are similarly social distancing can help foster social connection and development.
• Maintain connection digitally when in-person contact is not an option.³ Social groups, places of worship, and other activities have been agile in developing virtual communities. Communication by voice and/or video is thought to be more powerful than by written communication (text, email) alone.⁴ However, it is important to consider those who may have limited to no access to electronic methods.
• Encourage open communication with children about diversity and bias, and consider how our interactions with others may affect our children’s perspectives.⁵
• As providers, it is crucial that we address structural and institutional systems that negatively impact the health, safety, and access to care including our Black, indigenous, and people of color (BIPOC) and lesbian, gay, bisexual, transgender/transsexual, queer/questioning, intersex, and allied/asexual/aromantic/agender (LGBTQIA) patients.

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. Dr. Strange has no relevant financial disclosures. Email her at [email protected].

Online resources for parents and families

• Child Mind Institute: Coping With the Coronavirus Crisis: Supporting Your Kids.
• American Psychological Association: Talking with children about discrimination.
• Common Sense Media: Help with determining appropriateness of media for children.

Hotlines

• National Suicide Prevention Hotline: 1-800-273-8255
• GLBT National Hotline: 888-843-4564
• The California Peer-Run Warm Line: 1-855-845-7415
• Trevor Project: 866-488-7386 or text TREVOR to 1-202-304-1200
• Trans Lifeline: 877-565-8860
• Crisis Text Line: Text HOME to 741741

References

1. JAMA Pediatr. 2020 Apr 14. doi: 10.1001/jamapediatrics.2020.1456.

2. CDC: COVID-19 in Racial and Ethnic Minority Groups.

3. JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4469.

4. JAMA Intern Med. 2020 Apr 10. doi: 10.1001/jamainternmed.2020.1562.

5. American Psychological Association: Talking with children about discrimination.

A sense of safety and stability, both emotional and physical, is crucial in promoting the healthy development of youth. Between the global pandemic, need for social distancing, economic downturn, and increased awareness of racial disparities, for many this sense of stability has been rattled.

Ryan McVay/ThinkStock

School closures have led to a loss of social interaction, challenges to continued academic growth, and, for some students, lack of access to nutrition and increased food insecurity. For students with learning or mental health challenges, closures may have eliminated or significantly reduced desperately needed supports received in school.¹ While these trying circumstances have been difficult for many, the transition back to school in the fall also may be challenging because of the uncertainty about what this will look like and possible change in routine. Some students or their families may have anxiety about returning, either because of a history of adverse experiences at school such as bullying, or because of fears about exposure for themselves or others to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The past several months also brought about greater awareness of systemic racial disparities, whether as reflected in health care, education, or the criminal justice system. According to the Centers for Disease Control and Prevention data, Latinx and African-American individuals in the United States have had a threefold greater chance of contracting SARS-CoV-2 and have a twofold greater risk of death, compared with white people in the same communities.² Other social determinants of health – economic stability, education, social factors such as incarceration and discrimination, and neighborhood factors including access to healthy food – play a role in this vulnerability.

The pandemic has resulted in a need for social distancing, and as a result, isolation. Children and teens exposed to the news may have anxiety about what they see or hear. Additional pressures in the family can include economic uncertainty, loss of employment for the primary wage earner of the household, or stress related to family members being first responders.

Any one of these factors is a potentially significant stressor, so how do we best support youth to help them survive and hopefully thrive during this time?
 

• It is important to establish a sense of routine; this can help create a sense of stability and safety. Recognizing that circumstances are not the same as they were 5 or 6 months ago, encouraging structure should not come at the cost of preserving connection.
• Note positive behavior and choices made by children and make sure they know it was observed.
• Many children have experienced increased screen time with the lack of structure of the traditional school day or summer camp and extracurricular activities. Limiting screen time and being mindful of its potential impact on mood is prudent.
• Self-care for parents and guardians is important. This is clearly a marathon and not a sprint; parents’ caring for themselves will place them in a better position to support their children. This time is stressful for the adults of the household, let alone children who are learning self-regulation skills.
• Listen to children’s or teens’ concerns and share information in developmentally appropriate ways. It is okay to not have all of the answers.
• Balance fostering a sense of gratitude with not invalidating a child’s or teen’s experience. Showing empathy during this time is vital. While there may be other soccer seasons, it is normal to experience grief about the loss of experiences during this time.
• Parents and guardians know their children best, so it is prudent for them to be mindful of concerning changes such as an increase in sadness, anxiety, or irritability that negatively impacts daily functioning such as sleeping, eating, or relationships with family and friends.
• Promote social interactions with appropriate safeguards in place. Unfortunately, the number of SARS-CoV-2 infections is increasing in multiple states, and there is the potential to return to some of the previous restrictions. However, encouraging social interaction while following local guidelines and with cautions such as limiting the number of people present, meeting outside, or considering interacting with others who are similarly social distancing can help foster social connection and development.
• Maintain connection digitally when in-person contact is not an option.³ Social groups, places of worship, and other activities have been agile in developing virtual communities. Communication by voice and/or video is thought to be more powerful than by written communication (text, email) alone.⁴ However, it is important to consider those who may have limited to no access to electronic methods.
• Encourage open communication with children about diversity and bias, and consider how our interactions with others may affect our children’s perspectives.⁵
• As providers, it is crucial that we address structural and institutional systems that negatively impact the health, safety, and access to care including our Black, indigenous, and people of color (BIPOC) and lesbian, gay, bisexual, transgender/transsexual, queer/questioning, intersex, and allied/asexual/aromantic/agender (LGBTQIA) patients.

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. Dr. Strange has no relevant financial disclosures. Email her at [email protected].

Online resources for parents and families

• Child Mind Institute: Coping With the Coronavirus Crisis: Supporting Your Kids.
• American Psychological Association: Talking with children about discrimination.
• Common Sense Media: Help with determining appropriateness of media for children.

Hotlines

• National Suicide Prevention Hotline: 1-800-273-8255
• GLBT National Hotline: 888-843-4564
• The California Peer-Run Warm Line: 1-855-845-7415
• Trevor Project: 866-488-7386 or text TREVOR to 1-202-304-1200
• Trans Lifeline: 877-565-8860
• Crisis Text Line: Text HOME to 741741

References

1. JAMA Pediatr. 2020 Apr 14. doi: 10.1001/jamapediatrics.2020.1456.

2. CDC: COVID-19 in Racial and Ethnic Minority Groups.

3. JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4469.

4. JAMA Intern Med. 2020 Apr 10. doi: 10.1001/jamainternmed.2020.1562.

5. American Psychological Association: Talking with children about discrimination.

A sense of safety and stability, both emotional and physical, is crucial in promoting the healthy development of youth. Between the global pandemic, need for social distancing, economic downturn, and increased awareness of racial disparities, for many this sense of stability has been rattled.

Ryan McVay/ThinkStock

School closures have led to a loss of social interaction, challenges to continued academic growth, and, for some students, lack of access to nutrition and increased food insecurity. For students with learning or mental health challenges, closures may have eliminated or significantly reduced desperately needed supports received in school.¹ While these trying circumstances have been difficult for many, the transition back to school in the fall also may be challenging because of the uncertainty about what this will look like and possible change in routine. Some students or their families may have anxiety about returning, either because of a history of adverse experiences at school such as bullying, or because of fears about exposure for themselves or others to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The past several months also brought about greater awareness of systemic racial disparities, whether as reflected in health care, education, or the criminal justice system. According to the Centers for Disease Control and Prevention data, Latinx and African-American individuals in the United States have had a threefold greater chance of contracting SARS-CoV-2 and have a twofold greater risk of death, compared with white people in the same communities.² Other social determinants of health – economic stability, education, social factors such as incarceration and discrimination, and neighborhood factors including access to healthy food – play a role in this vulnerability.

The pandemic has resulted in a need for social distancing, and as a result, isolation. Children and teens exposed to the news may have anxiety about what they see or hear. Additional pressures in the family can include economic uncertainty, loss of employment for the primary wage earner of the household, or stress related to family members being first responders.

Any one of these factors is a potentially significant stressor, so how do we best support youth to help them survive and hopefully thrive during this time?
 

• It is important to establish a sense of routine; this can help create a sense of stability and safety. Recognizing that circumstances are not the same as they were 5 or 6 months ago, encouraging structure should not come at the cost of preserving connection.
• Note positive behavior and choices made by children and make sure they know it was observed.
• Many children have experienced increased screen time with the lack of structure of the traditional school day or summer camp and extracurricular activities. Limiting screen time and being mindful of its potential impact on mood is prudent.
• Self-care for parents and guardians is important. This is clearly a marathon and not a sprint; parents’ caring for themselves will place them in a better position to support their children. This time is stressful for the adults of the household, let alone children who are learning self-regulation skills.
• Listen to children’s or teens’ concerns and share information in developmentally appropriate ways. It is okay to not have all of the answers.
• Balance fostering a sense of gratitude with not invalidating a child’s or teen’s experience. Showing empathy during this time is vital. While there may be other soccer seasons, it is normal to experience grief about the loss of experiences during this time.
• Parents and guardians know their children best, so it is prudent for them to be mindful of concerning changes such as an increase in sadness, anxiety, or irritability that negatively impacts daily functioning such as sleeping, eating, or relationships with family and friends.
• Promote social interactions with appropriate safeguards in place. Unfortunately, the number of SARS-CoV-2 infections is increasing in multiple states, and there is the potential to return to some of the previous restrictions. However, encouraging social interaction while following local guidelines and with cautions such as limiting the number of people present, meeting outside, or considering interacting with others who are similarly social distancing can help foster social connection and development.
• Maintain connection digitally when in-person contact is not an option.³ Social groups, places of worship, and other activities have been agile in developing virtual communities. Communication by voice and/or video is thought to be more powerful than by written communication (text, email) alone.⁴ However, it is important to consider those who may have limited to no access to electronic methods.
• Encourage open communication with children about diversity and bias, and consider how our interactions with others may affect our children’s perspectives.⁵
• As providers, it is crucial that we address structural and institutional systems that negatively impact the health, safety, and access to care including our Black, indigenous, and people of color (BIPOC) and lesbian, gay, bisexual, transgender/transsexual, queer/questioning, intersex, and allied/asexual/aromantic/agender (LGBTQIA) patients.

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. Dr. Strange has no relevant financial disclosures. Email her at [email protected].

Online resources for parents and families

• Child Mind Institute: Coping With the Coronavirus Crisis: Supporting Your Kids.
• American Psychological Association: Talking with children about discrimination.
• Common Sense Media: Help with determining appropriateness of media for children.

Hotlines

• National Suicide Prevention Hotline: 1-800-273-8255
• GLBT National Hotline: 888-843-4564
• The California Peer-Run Warm Line: 1-855-845-7415
• Trevor Project: 866-488-7386 or text TREVOR to 1-202-304-1200
• Trans Lifeline: 877-565-8860
• Crisis Text Line: Text HOME to 741741

References

1. JAMA Pediatr. 2020 Apr 14. doi: 10.1001/jamapediatrics.2020.1456.

2. CDC: COVID-19 in Racial and Ethnic Minority Groups.

3. JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4469.

4. JAMA Intern Med. 2020 Apr 10. doi: 10.1001/jamainternmed.2020.1562.

5. American Psychological Association: Talking with children about discrimination.

Starting July 1, 2021, residents and fellows will be allowed a minimum 6 weeks away for medical leave or caregiving once during training, without having to use vacation or sick leave and without having to extend their training, the American Board of Medical Specialties has announced.

The “ABMS Policy on Parental, Caregiver and Family Leave” announced July 13 was developed after a report from the Accreditation Council for Graduate Medical Education’s Council of Review Committee Residents in June 2019.

Richard E. Hawkins, MD, ABMS President and CEO, said in a statement that “the growing shifts in viewpoints regarding work-life balance and parental roles had a great influence in the creation of this policy, which fosters an environment that supports our trainees’ ability to care not only for patients, but also for themselves and their families.”

Specifically, the time can be taken for birth and care of a newborn, adopting a child, or becoming a foster parent; care of a child, spouse, or parent with a serious health condition; or the trainee’s own serious health condition. The policy applies to member boards with training programs of at least 2 years.

Boards must communicate when a leave will require an official extension to avoid disruptions to a physician’s career trajectory, a delay in starting a fellowship, or moving into a salaried position.

Work/life balance was by far the biggest challenge reported in the Medscape Residents Lifestyle & Happiness Report 2019.

Several member boards had already implemented policies that offered more flexibility without unduly delaying board certification; now ABMS is extending that to all boards.

ABMS says member boards may limit the maximum time away in a single year or level of training and directed member boards to “make reasonable testing accommodations” – for example, by allowing candidates to take an exam provided the candidate completes all training requirements by a certain date.

Kristy Rialon, MD, an author of the ACGME report and assistant professor of surgery at Baylor College of Medicine and the Texas Children’s Hospital, both in Houston, noted the significance of the change in a news release.

“By virtue of their ages, residents and fellows – male and female – often find themselves having and raising children, as well as serving as family members’ caregivers,” Dr. Rialon said. “By adopting more realistic and compassionate approaches, the ABMS member boards will significantly improve the quality of life for residents and fellows. This also will support our female physicians, helping to narrow the gender gap in their career advancement by allowing for greater leave flexibility.”

A Medscape survey published July 15 said work-life balance was the No. 1 concern of female physicians, far outpacing pay.

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

Starting July 1, 2021, residents and fellows will be allowed a minimum 6 weeks away for medical leave or caregiving once during training, without having to use vacation or sick leave and without having to extend their training, the American Board of Medical Specialties has announced.

The “ABMS Policy on Parental, Caregiver and Family Leave” announced July 13 was developed after a report from the Accreditation Council for Graduate Medical Education’s Council of Review Committee Residents in June 2019.

Richard E. Hawkins, MD, ABMS President and CEO, said in a statement that “the growing shifts in viewpoints regarding work-life balance and parental roles had a great influence in the creation of this policy, which fosters an environment that supports our trainees’ ability to care not only for patients, but also for themselves and their families.”

Specifically, the time can be taken for birth and care of a newborn, adopting a child, or becoming a foster parent; care of a child, spouse, or parent with a serious health condition; or the trainee’s own serious health condition. The policy applies to member boards with training programs of at least 2 years.

Boards must communicate when a leave will require an official extension to avoid disruptions to a physician’s career trajectory, a delay in starting a fellowship, or moving into a salaried position.

Work/life balance was by far the biggest challenge reported in the Medscape Residents Lifestyle & Happiness Report 2019.

Several member boards had already implemented policies that offered more flexibility without unduly delaying board certification; now ABMS is extending that to all boards.

ABMS says member boards may limit the maximum time away in a single year or level of training and directed member boards to “make reasonable testing accommodations” – for example, by allowing candidates to take an exam provided the candidate completes all training requirements by a certain date.

Kristy Rialon, MD, an author of the ACGME report and assistant professor of surgery at Baylor College of Medicine and the Texas Children’s Hospital, both in Houston, noted the significance of the change in a news release.

“By virtue of their ages, residents and fellows – male and female – often find themselves having and raising children, as well as serving as family members’ caregivers,” Dr. Rialon said. “By adopting more realistic and compassionate approaches, the ABMS member boards will significantly improve the quality of life for residents and fellows. This also will support our female physicians, helping to narrow the gender gap in their career advancement by allowing for greater leave flexibility.”

A Medscape survey published July 15 said work-life balance was the No. 1 concern of female physicians, far outpacing pay.

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

Starting July 1, 2021, residents and fellows will be allowed a minimum 6 weeks away for medical leave or caregiving once during training, without having to use vacation or sick leave and without having to extend their training, the American Board of Medical Specialties has announced.

The “ABMS Policy on Parental, Caregiver and Family Leave” announced July 13 was developed after a report from the Accreditation Council for Graduate Medical Education’s Council of Review Committee Residents in June 2019.

Richard E. Hawkins, MD, ABMS President and CEO, said in a statement that “the growing shifts in viewpoints regarding work-life balance and parental roles had a great influence in the creation of this policy, which fosters an environment that supports our trainees’ ability to care not only for patients, but also for themselves and their families.”

Specifically, the time can be taken for birth and care of a newborn, adopting a child, or becoming a foster parent; care of a child, spouse, or parent with a serious health condition; or the trainee’s own serious health condition. The policy applies to member boards with training programs of at least 2 years.

Boards must communicate when a leave will require an official extension to avoid disruptions to a physician’s career trajectory, a delay in starting a fellowship, or moving into a salaried position.

Work/life balance was by far the biggest challenge reported in the Medscape Residents Lifestyle & Happiness Report 2019.

Several member boards had already implemented policies that offered more flexibility without unduly delaying board certification; now ABMS is extending that to all boards.

ABMS says member boards may limit the maximum time away in a single year or level of training and directed member boards to “make reasonable testing accommodations” – for example, by allowing candidates to take an exam provided the candidate completes all training requirements by a certain date.

Kristy Rialon, MD, an author of the ACGME report and assistant professor of surgery at Baylor College of Medicine and the Texas Children’s Hospital, both in Houston, noted the significance of the change in a news release.

“By virtue of their ages, residents and fellows – male and female – often find themselves having and raising children, as well as serving as family members’ caregivers,” Dr. Rialon said. “By adopting more realistic and compassionate approaches, the ABMS member boards will significantly improve the quality of life for residents and fellows. This also will support our female physicians, helping to narrow the gender gap in their career advancement by allowing for greater leave flexibility.”

A Medscape survey published July 15 said work-life balance was the No. 1 concern of female physicians, far outpacing pay.

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

A history of repetitive hits to the head (RHI), even without noticeable symptoms, is linked to a significantly increased risk of depression and poorer cognition later in life, new research shows.

“We found that a history of exposure to [repetitive hits to the head] from contact sports, military service, or physical abuse, as well as a history of TBI (traumatic brain injury), corresponded to more symptoms of later life depression and worse cognitive function,” lead author Michael Alosco, PhD, associate professor of neurology and codirector of the Boston University Alzheimer’s Disease Center Clinical Core, told Medscape Medical News.

He added that the findings underscore the importance of assessing repetitive head impacts (RHI).

The study was published online June 26 in Neurology.
 

Largest study to date

It is well known that sustaining a TBI is associated with worse later life cognition or mood problems, said Alosco. However, in the current research the investigators hypothesized that RHI may be a key driver of some of these outcomes, Alosco said.

Previous studies have been small or have only examined male former football players.

“What’s unique about our study is that we focused on a history of RHIs, and it is the largest study of its kind, incorporating over 30,000 males and females with different types of exposure to these RHIs.”

The researchers used data from the Brain Health Registry, an internet-based registry that longitudinally monitors cognition and functioning of participants (age 40 years and older).

Participants completed the Ohio State University TBI Identification Method (OSU TBI-ID) and answered a yes/no question: “Have you ever had a period of time in which you experienced multiple, repeated impacts to your head (eg, history of abuse, contact sports, military duty)?”

Participants also completed the Geriatric Depression Scale (GDS-15), the CogState Battery (CBB), and the Lumos Labs NeuroCognitive Performance Tests (NCPT). Demographic information included age, sex, race/ethnicity, and level of education.
 

Negative synergistic effect

Of the total sample (N = 13,323, mean age 62 years, 72.5% female, 88.6% White) 725 participants (5%) reported exposure to RHI, with contact sports as the most common cause, followed by physical abuse and then military duty; about 55% (7277 participants) reported TBI.

The researchers noted that 44.4% of those exposed to RHI and 70.3% of those who reported TBI were female. However, those with a history of contact sports were predominantly male and those reporting a history of abuse were predominantly women.

Among study participants who completed the GDS-15, 16.4% reported symptoms of depression, similar to rates reported among community-dwelling older adults.

Compared to the unexposed group, participants who reported TBI with loss of consciousness (LOC) and participants who reported TBI without LOC both had higher scores on the GDS-15 (beta = 0.75 [95% CI, 0.59-0.91] and beta = 0.43 [95% CI, 0.31-0.54], respectively).

A history of RHI was associated with an even higher depression score (beta = 1.24 [95% CI, 0.36-2.12).

Depression increased in tandem with increased exposure, with the lowest GDS-15 scores found in the unexposed group and subsequent increases in scores as exposure to RHI was introduced and TBI severity increased. The GDS scores were highest in those who had RHI plus TBI with LOC.

Participants with a history of RHI and/or TBI also had worse scores on tests of memory, learning, processing speed, and reaction time, compared with unexposed participants.

In particular, TBI with LOC had the most neuropsychological associations.

TBI without LOC had a negative effect on CogState tests measuring Identification and processing speed (beta = 0.004 [95% CI, 0-0.01] and beta = 0.004 [95% CI, 0.0002-0.01], respectively), whereas RHI predicted a worse processing speed score (beta = .02 [95% CI, 0.01-0.05]).

The presence of both RHI and TBI (with or without LOC) had a “synergistic negative effect” on neuropsychological performance, with a “consistent statistically significant finding” for worse neuropsychological test performance for those who had RHI and TBI with LOC, compared with those who had not sustained RHI.

Alosco said the findings highlight the need for clinicians to educate and inform parents/guardians of kids playing (or considering playing) contact sports about the research and potential risks associated with these activities.

“We have to ask the question: ‘Does it make sense to expose ourselves to these repeated hits to the heads?’ If we want to prevent long-term problems, one way is not to expose [people] to these hits. Everyone takes risks in life with everything, but the more we can understand and mitigate the risks, the better,” Alosco said.
 

“A significant contribution”

Commenting on the findings for Medscape Medical News, Temitayo Oyegbile-Chidi, MD, PhD, a pediatric neurologist with Health Peak Inc, McLean, Virginia, and a member of the American Academy of Neurology, said the study “makes a significant contribution to the literature, as neurologists who specialized in TBI have long yearned to understand the long-term effects of repeated head impact on the brain and cognition.”

Clinicians should “inquire about a history of prior head impacts on all our patients, regardless of age, especially if they are experiencing or showing signs of unexpected cognitive dysfunction or mental health concerns,” said Oyegbile-Chidi, who was not involved with the study.

For those who have sustained single or repeated head impacts with or without associated LOC in the past, “it is important … to keep in mind that depression and cognitive dysfunction may persist or present even many years after the impact was sustained,” she added.

The study was supported by a grant from the National Institutes of Health. Alosco has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Oyegbile-Chidi has disclosed no relevant financial relationships.

A history of repetitive hits to the head (RHI), even without noticeable symptoms, is linked to a significantly increased risk of depression and poorer cognition later in life, new research shows.

“We found that a history of exposure to [repetitive hits to the head] from contact sports, military service, or physical abuse, as well as a history of TBI (traumatic brain injury), corresponded to more symptoms of later life depression and worse cognitive function,” lead author Michael Alosco, PhD, associate professor of neurology and codirector of the Boston University Alzheimer’s Disease Center Clinical Core, told Medscape Medical News.

He added that the findings underscore the importance of assessing repetitive head impacts (RHI).

The study was published online June 26 in Neurology.
 

Largest study to date

It is well known that sustaining a TBI is associated with worse later life cognition or mood problems, said Alosco. However, in the current research the investigators hypothesized that RHI may be a key driver of some of these outcomes, Alosco said.

Previous studies have been small or have only examined male former football players.

“What’s unique about our study is that we focused on a history of RHIs, and it is the largest study of its kind, incorporating over 30,000 males and females with different types of exposure to these RHIs.”

The researchers used data from the Brain Health Registry, an internet-based registry that longitudinally monitors cognition and functioning of participants (age 40 years and older).

Participants completed the Ohio State University TBI Identification Method (OSU TBI-ID) and answered a yes/no question: “Have you ever had a period of time in which you experienced multiple, repeated impacts to your head (eg, history of abuse, contact sports, military duty)?”

Participants also completed the Geriatric Depression Scale (GDS-15), the CogState Battery (CBB), and the Lumos Labs NeuroCognitive Performance Tests (NCPT). Demographic information included age, sex, race/ethnicity, and level of education.
 

Negative synergistic effect

Of the total sample (N = 13,323, mean age 62 years, 72.5% female, 88.6% White) 725 participants (5%) reported exposure to RHI, with contact sports as the most common cause, followed by physical abuse and then military duty; about 55% (7277 participants) reported TBI.

The researchers noted that 44.4% of those exposed to RHI and 70.3% of those who reported TBI were female. However, those with a history of contact sports were predominantly male and those reporting a history of abuse were predominantly women.

Among study participants who completed the GDS-15, 16.4% reported symptoms of depression, similar to rates reported among community-dwelling older adults.

Compared to the unexposed group, participants who reported TBI with loss of consciousness (LOC) and participants who reported TBI without LOC both had higher scores on the GDS-15 (beta = 0.75 [95% CI, 0.59-0.91] and beta = 0.43 [95% CI, 0.31-0.54], respectively).

A history of RHI was associated with an even higher depression score (beta = 1.24 [95% CI, 0.36-2.12).

Depression increased in tandem with increased exposure, with the lowest GDS-15 scores found in the unexposed group and subsequent increases in scores as exposure to RHI was introduced and TBI severity increased. The GDS scores were highest in those who had RHI plus TBI with LOC.

Participants with a history of RHI and/or TBI also had worse scores on tests of memory, learning, processing speed, and reaction time, compared with unexposed participants.

In particular, TBI with LOC had the most neuropsychological associations.

TBI without LOC had a negative effect on CogState tests measuring Identification and processing speed (beta = 0.004 [95% CI, 0-0.01] and beta = 0.004 [95% CI, 0.0002-0.01], respectively), whereas RHI predicted a worse processing speed score (beta = .02 [95% CI, 0.01-0.05]).

The presence of both RHI and TBI (with or without LOC) had a “synergistic negative effect” on neuropsychological performance, with a “consistent statistically significant finding” for worse neuropsychological test performance for those who had RHI and TBI with LOC, compared with those who had not sustained RHI.

Alosco said the findings highlight the need for clinicians to educate and inform parents/guardians of kids playing (or considering playing) contact sports about the research and potential risks associated with these activities.

“We have to ask the question: ‘Does it make sense to expose ourselves to these repeated hits to the heads?’ If we want to prevent long-term problems, one way is not to expose [people] to these hits. Everyone takes risks in life with everything, but the more we can understand and mitigate the risks, the better,” Alosco said.
 

“A significant contribution”

Commenting on the findings for Medscape Medical News, Temitayo Oyegbile-Chidi, MD, PhD, a pediatric neurologist with Health Peak Inc, McLean, Virginia, and a member of the American Academy of Neurology, said the study “makes a significant contribution to the literature, as neurologists who specialized in TBI have long yearned to understand the long-term effects of repeated head impact on the brain and cognition.”

Clinicians should “inquire about a history of prior head impacts on all our patients, regardless of age, especially if they are experiencing or showing signs of unexpected cognitive dysfunction or mental health concerns,” said Oyegbile-Chidi, who was not involved with the study.

For those who have sustained single or repeated head impacts with or without associated LOC in the past, “it is important … to keep in mind that depression and cognitive dysfunction may persist or present even many years after the impact was sustained,” she added.

The study was supported by a grant from the National Institutes of Health. Alosco has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Oyegbile-Chidi has disclosed no relevant financial relationships.

A history of repetitive hits to the head (RHI), even without noticeable symptoms, is linked to a significantly increased risk of depression and poorer cognition later in life, new research shows.

“We found that a history of exposure to [repetitive hits to the head] from contact sports, military service, or physical abuse, as well as a history of TBI (traumatic brain injury), corresponded to more symptoms of later life depression and worse cognitive function,” lead author Michael Alosco, PhD, associate professor of neurology and codirector of the Boston University Alzheimer’s Disease Center Clinical Core, told Medscape Medical News.

He added that the findings underscore the importance of assessing repetitive head impacts (RHI).

The study was published online June 26 in Neurology.
 

Largest study to date

It is well known that sustaining a TBI is associated with worse later life cognition or mood problems, said Alosco. However, in the current research the investigators hypothesized that RHI may be a key driver of some of these outcomes, Alosco said.

Previous studies have been small or have only examined male former football players.

“What’s unique about our study is that we focused on a history of RHIs, and it is the largest study of its kind, incorporating over 30,000 males and females with different types of exposure to these RHIs.”

The researchers used data from the Brain Health Registry, an internet-based registry that longitudinally monitors cognition and functioning of participants (age 40 years and older).

Participants completed the Ohio State University TBI Identification Method (OSU TBI-ID) and answered a yes/no question: “Have you ever had a period of time in which you experienced multiple, repeated impacts to your head (eg, history of abuse, contact sports, military duty)?”

Participants also completed the Geriatric Depression Scale (GDS-15), the CogState Battery (CBB), and the Lumos Labs NeuroCognitive Performance Tests (NCPT). Demographic information included age, sex, race/ethnicity, and level of education.
 

Negative synergistic effect

Of the total sample (N = 13,323, mean age 62 years, 72.5% female, 88.6% White) 725 participants (5%) reported exposure to RHI, with contact sports as the most common cause, followed by physical abuse and then military duty; about 55% (7277 participants) reported TBI.

The researchers noted that 44.4% of those exposed to RHI and 70.3% of those who reported TBI were female. However, those with a history of contact sports were predominantly male and those reporting a history of abuse were predominantly women.

Among study participants who completed the GDS-15, 16.4% reported symptoms of depression, similar to rates reported among community-dwelling older adults.

Compared to the unexposed group, participants who reported TBI with loss of consciousness (LOC) and participants who reported TBI without LOC both had higher scores on the GDS-15 (beta = 0.75 [95% CI, 0.59-0.91] and beta = 0.43 [95% CI, 0.31-0.54], respectively).

A history of RHI was associated with an even higher depression score (beta = 1.24 [95% CI, 0.36-2.12).

Depression increased in tandem with increased exposure, with the lowest GDS-15 scores found in the unexposed group and subsequent increases in scores as exposure to RHI was introduced and TBI severity increased. The GDS scores were highest in those who had RHI plus TBI with LOC.

Participants with a history of RHI and/or TBI also had worse scores on tests of memory, learning, processing speed, and reaction time, compared with unexposed participants.

In particular, TBI with LOC had the most neuropsychological associations.

TBI without LOC had a negative effect on CogState tests measuring Identification and processing speed (beta = 0.004 [95% CI, 0-0.01] and beta = 0.004 [95% CI, 0.0002-0.01], respectively), whereas RHI predicted a worse processing speed score (beta = .02 [95% CI, 0.01-0.05]).

The presence of both RHI and TBI (with or without LOC) had a “synergistic negative effect” on neuropsychological performance, with a “consistent statistically significant finding” for worse neuropsychological test performance for those who had RHI and TBI with LOC, compared with those who had not sustained RHI.

Alosco said the findings highlight the need for clinicians to educate and inform parents/guardians of kids playing (or considering playing) contact sports about the research and potential risks associated with these activities.

“We have to ask the question: ‘Does it make sense to expose ourselves to these repeated hits to the heads?’ If we want to prevent long-term problems, one way is not to expose [people] to these hits. Everyone takes risks in life with everything, but the more we can understand and mitigate the risks, the better,” Alosco said.
 

“A significant contribution”

Commenting on the findings for Medscape Medical News, Temitayo Oyegbile-Chidi, MD, PhD, a pediatric neurologist with Health Peak Inc, McLean, Virginia, and a member of the American Academy of Neurology, said the study “makes a significant contribution to the literature, as neurologists who specialized in TBI have long yearned to understand the long-term effects of repeated head impact on the brain and cognition.”

Clinicians should “inquire about a history of prior head impacts on all our patients, regardless of age, especially if they are experiencing or showing signs of unexpected cognitive dysfunction or mental health concerns,” said Oyegbile-Chidi, who was not involved with the study.

For those who have sustained single or repeated head impacts with or without associated LOC in the past, “it is important … to keep in mind that depression and cognitive dysfunction may persist or present even many years after the impact was sustained,” she added.

The study was supported by a grant from the National Institutes of Health. Alosco has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Oyegbile-Chidi has disclosed no relevant financial relationships.

With the COVID-19 pandemic, we are experiencing a once-in-a-100-year event. Dr. Steven A. Schulz, who is serving children on the front line in upstate New York, and I outline some of the challenges primary care pediatricians have been facing and solutions that have succeeded.

Reduction in direct patient care and its consequences

Geber86/E+

Because of the unknowns of COVID-19, many parents have not wanted to bring their children to a medical office because of fear of contracting SARS-CoV-2. At the same time, pediatricians have restricted in-person visits to prevent spread of SARS-CoV-2 and to help flatten the curve of infection. Use of pediatric medical professional services, compared with last year, dropped by 52% in March 2020 and by 58% in April, according to FAIR Health, a nonprofit organization that manages a database of 31 million claims. This is resulting in decreased immunization rates, which increases concern for secondary spikes of other preventable illnesses; for example, data from the Centers for Disease Control and Prevention showed that, from mid-March to mid-April 2020, physicians in the Vaccines for Children program ordered 2.5 million fewer doses of vaccines and 250,000 fewer doses of measles-containing vaccines, compared with the same period in 2019. Fewer children are being seen for well visits, which means opportunities are lost for adequate monitoring of growth, development, physical wellness, and social determinants of health.

This is occurring at a time when families have been experiencing increased stress in terms of finances, social isolation, finding adequate child care, and serving as parent, teacher, and breadwinner. An increase in injuries is occurring because of inadequate parental supervision because many parents have been distracted while working from home. An increase in cases of severe abuse is occurring because schools, child care providers, physicians, and other mandated reporters in the community have decreased interaction with children. Children’s Hospital Colorado in Colorado Springs saw a 118% increase in the number of trauma cases in its ED between January and April 2020. Some of these were accidental injuries caused by falls or bicycle accidents, but there was a 200% increase in nonaccidental trauma, which was associated with a steep fall in calls to the state’s child abuse hotline. Academic gains are being lost, and there has been worry for a prolonged “summer slide” risk, especially for children living in poverty and children with developmental disabilities.

The COVID-19 pandemic also is affecting physicians and staff. As frontline personnel, we are at risk to contract the virus, and news media reminds us of severe illness and deaths among health care workers. The pandemic is affecting financial viability; estimated revenue of pediatric offices fell by 45% in March 2020 and 48% in April, compared with the previous year, according to FAIR Health. Nurses and staff have been furloughed. Practices have had to apply for grants and Paycheck Protection Program funds while extending credit lines.
 

Limited testing capability for SARS-CoV-2

Testing for SARS-CoV-2 has been variably available. There have been problems with false positive and especially false negative results (BMJ. 2020 May 12. doi: 10.1136/bmj.m1808).The best specimen collection method has yet to be determined. Blood testing for antibody has been touted, but it remains unclear if there is clinical benefit because a positive result offers no guarantee of immunity, and immunity may quickly wane. Perhaps widespread primary care office–based testing will be in place by the fall, with hope for future reliable point of care results.

Evolving knowledge regarding SARS-CoV-2 and MIS-C

It initially was thought that children were relatively spared from serious illness caused by COVID-19. Then reports of cases of newly identified multisystem inflammatory syndrome of children occurred. It has been unclear how children contribute to the spread of COVID-19 illness, although emerging evidence indicates it is lower than adult transmission. What will happen when children return to school and daycare in the fall?

The challenges have led to creative solutions for how to deliver care.
 

Adapting to telehealth to provide care

At least for the short term, HIPAA regulations have been relaxed to allow for video visits using platforms such as FaceTime, Skype, Zoom, Doximity, and Doxy.me. Some of these platforms are HIPAA compliant and will be long-term solutions; however, electronic medical record portals allowing for video visits are the more secure option, according to HIPAA.

It has been a learning experience to see what can be accomplished with a video visit. Taking a history and visual examination of injuries and rashes has been possible. Addressing mental health concerns through the video exchange generally has been effective.

However, video visits change the provider-patient interpersonal dynamic and offer only visual exam capabilities, compared with an in-person visit. We cannot look in ears, palpate a liver and spleen, touch and examine a joint or bone, or feel a rash. Video visits also are dependent on the quality of patient Internet access, sufficient data plans, and mutual capabilities to address the inevitable technological glitches on the provider’s end as well. Expanding information technology infrastructure ability and added licensure costs have occurred. Practices and health systems have been working with insurance companies to ensure telephone and video visits are reimbursed on a comparable level to in-office visits.
 

A new type of office visit and developing appropriate safety plans

As understanding of SARS-CoV-2 transmission evolved, office work flows have been modified. Patients must be universally screened prior to arrival during appointment scheduling for well and illness visits. Patients aged older than 2 years and caregivers must wear masks on entering the facility. In many practices, patients are scheduled during specific sick or well visit time slots throughout the day. Waiting rooms chairs need to be spaced for 6-foot social distancing, and cars in the parking lot often serve as waiting rooms until staff can meet patients at the door and take them to the exam room. Alternate entrances, car-side exams, and drive-by and/or tent testing facilities often have become part of the new normal everyday practice. Creating virtual visit time blocks in provider’s schedules has allowed for decreased office congestion. Patients often are checked out from their room, as opposed to waiting in a line at a check out desk. Nurse triage protocols also have been adapted and enhanced to meet needs and concerns.

With the need for summer physicals and many regions opening up, a gradual return toward baseline has been evolving, although some of the twists of a “new normal” will stay in place. The new normal has been for providers and staff to wear surgical masks and face shields; sometimes N95 masks, gloves, and gowns have been needed. Cleaning rooms and equipment between patient visits has become a major, new time-consuming task. Acquiring and maintaining adequate supplies has been a challenge.
 

Summary

The American Academy of Pediatrics, CDC, and state and local health departments have been providing informative and regular updates, webinars, and best practices guidelines. Pediatricians, community organizations, schools, and mental health professionals have been collaborating, overcoming hurdles, and working together to help mitigate the effects of the pandemic on children, their families, and our communities. Continued education, cooperation, and adaptation will be needed in the months ahead. If there is a silver lining to this pandemic experience, it may be that families have grown closer together as they sheltered in place (and we have grown closer to our own families as well). One day perhaps a child who lived through this pandemic might be asked what it was like, and their recollection might be that it was a wonderful time because their parents stayed home all the time, took care of them, taught them their school work, and took lots of long family walks.

Dr. Schulz is pediatric medical director, Rochester (N.Y.) Regional Health. Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz and Dr. Pichichero said they have no relevant financial disclosures. Email them at [email protected].

This article was updated 7/16/2020.

With the COVID-19 pandemic, we are experiencing a once-in-a-100-year event. Dr. Steven A. Schulz, who is serving children on the front line in upstate New York, and I outline some of the challenges primary care pediatricians have been facing and solutions that have succeeded.

Reduction in direct patient care and its consequences

Geber86/E+

Because of the unknowns of COVID-19, many parents have not wanted to bring their children to a medical office because of fear of contracting SARS-CoV-2. At the same time, pediatricians have restricted in-person visits to prevent spread of SARS-CoV-2 and to help flatten the curve of infection. Use of pediatric medical professional services, compared with last year, dropped by 52% in March 2020 and by 58% in April, according to FAIR Health, a nonprofit organization that manages a database of 31 million claims. This is resulting in decreased immunization rates, which increases concern for secondary spikes of other preventable illnesses; for example, data from the Centers for Disease Control and Prevention showed that, from mid-March to mid-April 2020, physicians in the Vaccines for Children program ordered 2.5 million fewer doses of vaccines and 250,000 fewer doses of measles-containing vaccines, compared with the same period in 2019. Fewer children are being seen for well visits, which means opportunities are lost for adequate monitoring of growth, development, physical wellness, and social determinants of health.

This is occurring at a time when families have been experiencing increased stress in terms of finances, social isolation, finding adequate child care, and serving as parent, teacher, and breadwinner. An increase in injuries is occurring because of inadequate parental supervision because many parents have been distracted while working from home. An increase in cases of severe abuse is occurring because schools, child care providers, physicians, and other mandated reporters in the community have decreased interaction with children. Children’s Hospital Colorado in Colorado Springs saw a 118% increase in the number of trauma cases in its ED between January and April 2020. Some of these were accidental injuries caused by falls or bicycle accidents, but there was a 200% increase in nonaccidental trauma, which was associated with a steep fall in calls to the state’s child abuse hotline. Academic gains are being lost, and there has been worry for a prolonged “summer slide” risk, especially for children living in poverty and children with developmental disabilities.

The COVID-19 pandemic also is affecting physicians and staff. As frontline personnel, we are at risk to contract the virus, and news media reminds us of severe illness and deaths among health care workers. The pandemic is affecting financial viability; estimated revenue of pediatric offices fell by 45% in March 2020 and 48% in April, compared with the previous year, according to FAIR Health. Nurses and staff have been furloughed. Practices have had to apply for grants and Paycheck Protection Program funds while extending credit lines.
 

Limited testing capability for SARS-CoV-2

Testing for SARS-CoV-2 has been variably available. There have been problems with false positive and especially false negative results (BMJ. 2020 May 12. doi: 10.1136/bmj.m1808).The best specimen collection method has yet to be determined. Blood testing for antibody has been touted, but it remains unclear if there is clinical benefit because a positive result offers no guarantee of immunity, and immunity may quickly wane. Perhaps widespread primary care office–based testing will be in place by the fall, with hope for future reliable point of care results.

Evolving knowledge regarding SARS-CoV-2 and MIS-C

It initially was thought that children were relatively spared from serious illness caused by COVID-19. Then reports of cases of newly identified multisystem inflammatory syndrome of children occurred. It has been unclear how children contribute to the spread of COVID-19 illness, although emerging evidence indicates it is lower than adult transmission. What will happen when children return to school and daycare in the fall?

The challenges have led to creative solutions for how to deliver care.
 

Adapting to telehealth to provide care

At least for the short term, HIPAA regulations have been relaxed to allow for video visits using platforms such as FaceTime, Skype, Zoom, Doximity, and Doxy.me. Some of these platforms are HIPAA compliant and will be long-term solutions; however, electronic medical record portals allowing for video visits are the more secure option, according to HIPAA.

It has been a learning experience to see what can be accomplished with a video visit. Taking a history and visual examination of injuries and rashes has been possible. Addressing mental health concerns through the video exchange generally has been effective.

However, video visits change the provider-patient interpersonal dynamic and offer only visual exam capabilities, compared with an in-person visit. We cannot look in ears, palpate a liver and spleen, touch and examine a joint or bone, or feel a rash. Video visits also are dependent on the quality of patient Internet access, sufficient data plans, and mutual capabilities to address the inevitable technological glitches on the provider’s end as well. Expanding information technology infrastructure ability and added licensure costs have occurred. Practices and health systems have been working with insurance companies to ensure telephone and video visits are reimbursed on a comparable level to in-office visits.
 

A new type of office visit and developing appropriate safety plans

As understanding of SARS-CoV-2 transmission evolved, office work flows have been modified. Patients must be universally screened prior to arrival during appointment scheduling for well and illness visits. Patients aged older than 2 years and caregivers must wear masks on entering the facility. In many practices, patients are scheduled during specific sick or well visit time slots throughout the day. Waiting rooms chairs need to be spaced for 6-foot social distancing, and cars in the parking lot often serve as waiting rooms until staff can meet patients at the door and take them to the exam room. Alternate entrances, car-side exams, and drive-by and/or tent testing facilities often have become part of the new normal everyday practice. Creating virtual visit time blocks in provider’s schedules has allowed for decreased office congestion. Patients often are checked out from their room, as opposed to waiting in a line at a check out desk. Nurse triage protocols also have been adapted and enhanced to meet needs and concerns.

With the need for summer physicals and many regions opening up, a gradual return toward baseline has been evolving, although some of the twists of a “new normal” will stay in place. The new normal has been for providers and staff to wear surgical masks and face shields; sometimes N95 masks, gloves, and gowns have been needed. Cleaning rooms and equipment between patient visits has become a major, new time-consuming task. Acquiring and maintaining adequate supplies has been a challenge.
 

Summary

The American Academy of Pediatrics, CDC, and state and local health departments have been providing informative and regular updates, webinars, and best practices guidelines. Pediatricians, community organizations, schools, and mental health professionals have been collaborating, overcoming hurdles, and working together to help mitigate the effects of the pandemic on children, their families, and our communities. Continued education, cooperation, and adaptation will be needed in the months ahead. If there is a silver lining to this pandemic experience, it may be that families have grown closer together as they sheltered in place (and we have grown closer to our own families as well). One day perhaps a child who lived through this pandemic might be asked what it was like, and their recollection might be that it was a wonderful time because their parents stayed home all the time, took care of them, taught them their school work, and took lots of long family walks.

Dr. Schulz is pediatric medical director, Rochester (N.Y.) Regional Health. Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz and Dr. Pichichero said they have no relevant financial disclosures. Email them at [email protected].

This article was updated 7/16/2020.

With the COVID-19 pandemic, we are experiencing a once-in-a-100-year event. Dr. Steven A. Schulz, who is serving children on the front line in upstate New York, and I outline some of the challenges primary care pediatricians have been facing and solutions that have succeeded.

Reduction in direct patient care and its consequences

Geber86/E+

Because of the unknowns of COVID-19, many parents have not wanted to bring their children to a medical office because of fear of contracting SARS-CoV-2. At the same time, pediatricians have restricted in-person visits to prevent spread of SARS-CoV-2 and to help flatten the curve of infection. Use of pediatric medical professional services, compared with last year, dropped by 52% in March 2020 and by 58% in April, according to FAIR Health, a nonprofit organization that manages a database of 31 million claims. This is resulting in decreased immunization rates, which increases concern for secondary spikes of other preventable illnesses; for example, data from the Centers for Disease Control and Prevention showed that, from mid-March to mid-April 2020, physicians in the Vaccines for Children program ordered 2.5 million fewer doses of vaccines and 250,000 fewer doses of measles-containing vaccines, compared with the same period in 2019. Fewer children are being seen for well visits, which means opportunities are lost for adequate monitoring of growth, development, physical wellness, and social determinants of health.

This is occurring at a time when families have been experiencing increased stress in terms of finances, social isolation, finding adequate child care, and serving as parent, teacher, and breadwinner. An increase in injuries is occurring because of inadequate parental supervision because many parents have been distracted while working from home. An increase in cases of severe abuse is occurring because schools, child care providers, physicians, and other mandated reporters in the community have decreased interaction with children. Children’s Hospital Colorado in Colorado Springs saw a 118% increase in the number of trauma cases in its ED between January and April 2020. Some of these were accidental injuries caused by falls or bicycle accidents, but there was a 200% increase in nonaccidental trauma, which was associated with a steep fall in calls to the state’s child abuse hotline. Academic gains are being lost, and there has been worry for a prolonged “summer slide” risk, especially for children living in poverty and children with developmental disabilities.

The COVID-19 pandemic also is affecting physicians and staff. As frontline personnel, we are at risk to contract the virus, and news media reminds us of severe illness and deaths among health care workers. The pandemic is affecting financial viability; estimated revenue of pediatric offices fell by 45% in March 2020 and 48% in April, compared with the previous year, according to FAIR Health. Nurses and staff have been furloughed. Practices have had to apply for grants and Paycheck Protection Program funds while extending credit lines.
 

Limited testing capability for SARS-CoV-2

Testing for SARS-CoV-2 has been variably available. There have been problems with false positive and especially false negative results (BMJ. 2020 May 12. doi: 10.1136/bmj.m1808).The best specimen collection method has yet to be determined. Blood testing for antibody has been touted, but it remains unclear if there is clinical benefit because a positive result offers no guarantee of immunity, and immunity may quickly wane. Perhaps widespread primary care office–based testing will be in place by the fall, with hope for future reliable point of care results.

Evolving knowledge regarding SARS-CoV-2 and MIS-C

It initially was thought that children were relatively spared from serious illness caused by COVID-19. Then reports of cases of newly identified multisystem inflammatory syndrome of children occurred. It has been unclear how children contribute to the spread of COVID-19 illness, although emerging evidence indicates it is lower than adult transmission. What will happen when children return to school and daycare in the fall?

The challenges have led to creative solutions for how to deliver care.
 

Adapting to telehealth to provide care

At least for the short term, HIPAA regulations have been relaxed to allow for video visits using platforms such as FaceTime, Skype, Zoom, Doximity, and Doxy.me. Some of these platforms are HIPAA compliant and will be long-term solutions; however, electronic medical record portals allowing for video visits are the more secure option, according to HIPAA.

It has been a learning experience to see what can be accomplished with a video visit. Taking a history and visual examination of injuries and rashes has been possible. Addressing mental health concerns through the video exchange generally has been effective.

However, video visits change the provider-patient interpersonal dynamic and offer only visual exam capabilities, compared with an in-person visit. We cannot look in ears, palpate a liver and spleen, touch and examine a joint or bone, or feel a rash. Video visits also are dependent on the quality of patient Internet access, sufficient data plans, and mutual capabilities to address the inevitable technological glitches on the provider’s end as well. Expanding information technology infrastructure ability and added licensure costs have occurred. Practices and health systems have been working with insurance companies to ensure telephone and video visits are reimbursed on a comparable level to in-office visits.
 

A new type of office visit and developing appropriate safety plans

As understanding of SARS-CoV-2 transmission evolved, office work flows have been modified. Patients must be universally screened prior to arrival during appointment scheduling for well and illness visits. Patients aged older than 2 years and caregivers must wear masks on entering the facility. In many practices, patients are scheduled during specific sick or well visit time slots throughout the day. Waiting rooms chairs need to be spaced for 6-foot social distancing, and cars in the parking lot often serve as waiting rooms until staff can meet patients at the door and take them to the exam room. Alternate entrances, car-side exams, and drive-by and/or tent testing facilities often have become part of the new normal everyday practice. Creating virtual visit time blocks in provider’s schedules has allowed for decreased office congestion. Patients often are checked out from their room, as opposed to waiting in a line at a check out desk. Nurse triage protocols also have been adapted and enhanced to meet needs and concerns.

With the need for summer physicals and many regions opening up, a gradual return toward baseline has been evolving, although some of the twists of a “new normal” will stay in place. The new normal has been for providers and staff to wear surgical masks and face shields; sometimes N95 masks, gloves, and gowns have been needed. Cleaning rooms and equipment between patient visits has become a major, new time-consuming task. Acquiring and maintaining adequate supplies has been a challenge.
 

Summary

The American Academy of Pediatrics, CDC, and state and local health departments have been providing informative and regular updates, webinars, and best practices guidelines. Pediatricians, community organizations, schools, and mental health professionals have been collaborating, overcoming hurdles, and working together to help mitigate the effects of the pandemic on children, their families, and our communities. Continued education, cooperation, and adaptation will be needed in the months ahead. If there is a silver lining to this pandemic experience, it may be that families have grown closer together as they sheltered in place (and we have grown closer to our own families as well). One day perhaps a child who lived through this pandemic might be asked what it was like, and their recollection might be that it was a wonderful time because their parents stayed home all the time, took care of them, taught them their school work, and took lots of long family walks.

Dr. Schulz is pediatric medical director, Rochester (N.Y.) Regional Health. Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz and Dr. Pichichero said they have no relevant financial disclosures. Email them at [email protected].

This article was updated 7/16/2020.

As the Food and Drug Administration focuses on other issues, companies, both big and small, are looking to boost physician and consumer interest in their “medical foods” – products that fall somewhere between drugs and supplements and promise to mitigate symptoms, or even address underlying pathologies, of a range of diseases.

Manufacturers now market an array of medical foods, ranging from powders and capsules for Alzheimer disease to low-protein spaghetti for chronic kidney disease (CKD). The FDA has not been completely absent; it takes a narrow view of what medical conditions qualify for treatment with food products and has warned some manufacturers that their misbranded products are acting more like unapproved drugs.

By the FDA’s definition, medical food is limited to products that provide crucial therapy for patients with inborn errors of metabolism (IEM). An example is specialized baby formula for infants with phenylketonuria. Unlike supplements, medical foods are supposed to be used under the supervision of a physician. This has prompted some sales reps to turn up in the clinic, and most manufacturers have online approval forms for doctors to sign. Manufacturers, advisers, and regulators were interviewed for a closer look at this burgeoning industry.
 

The market

The global market for medical foods – about $18 billion in 2019 – is expected to grow steadily in the near future. It is drawing more interest, especially in Europe, where medical foods are more accepted by physicians and consumers, Meghan Donnelly, MS, RDN, said in an interview. She is a registered dietitian who conducts physician outreach in the United States for Flavis, a division of Dr. Schär. That company, based in northern Italy, started out targeting IEMs but now also sells gluten-free foods for celiac disease and low-protein foods for CKD.

It is still a niche market in the United States – and isn’t likely to ever approach the size of the supplement market, according to Marcus Charuvastra, the managing director of Targeted Medical Pharma, which markets Theramine capsules for pain management, among many other products. But it could still be a big win for a manufacturer if they get a small slice of a big market, such as for Alzheimer disease.
 

Defining medical food

According to an update of the Orphan Drug Act in 1988, a medical food is “a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.” The FDA issued regulations to accompany that law in 1993 but has since only issued a guidance document that is not legally binding.

Medical foods are not drugs and they are not supplements (the latter are intended only for healthy people). The FDA doesn’t require formal approval of a medical food, but, by law, the ingredients must be generally recognized as safe, and manufacturers must follow good manufacturing practices. However, the agency has taken a narrow view of what conditions require medical foods.

Policing medical foods hasn’t been a priority for the FDA, which is why there has been a proliferation of products that don’t meet the FDA’s view of the statutory definition of medical foods, according to Miriam Guggenheim, a food and drug law attorney in Washington, D.C. The FDA usually takes enforcement action when it sees a risk to the public’s health.

The agency’s stance has led to confusion – among manufacturers, physicians, consumers, and even regulators – making the market a kind of Wild West, according to Paul Hyman, a Washington, D.C.–based attorney who has represented medical food companies.

George A. Burdock, PhD, an Orlando-based regulatory consultant who has worked with medical food makers, believes the FDA will be forced to expand their narrow definition. He foresees a reconsideration of many medical food products in light of an October 2019 White House executive order prohibiting federal agencies from issuing guidance in lieu of rules.
 

Manufacturers and the FDA differ

One example of a product about which regulators and manufacturers differ is Theramine, which is described as “specially designed to supply the nervous system with the fuel it needs to meet the altered metabolic requirements of chronic pain and inflammatory disorders.”

It is not considered a medical food by the FDA, and the company has had numerous discussions with the agency about their diverging views, according to Mr. Charuvastra. “We’ve had our warning letters and we’ve had our sit downs, and we just had an inspection.”

Targeted Medical Pharma continues to market its products as medical foods but steers away from making any claims that they are like drugs, he said.

Confusion about medical foods has been exposed in the California Workers’ Compensation System by Leslie Wilson, PhD, and colleagues at the University of California, San Francisco. They found that physicians regularly wrote medical food prescriptions for non–FDA-approved uses and that the system reimbursed the majority of the products at a cost of $15.5 million from 2011 to 2013. More than half of these prescriptions were for Theramine.

Dr. Wilson reported that, for most products, no evidence supported effectiveness, and they were frequently mislabeled – for all 36 that were studied, submissions for reimbursement were made using a National Drug Code, an impossibility because medical foods are not drugs, and 14 were labeled “Rx only.”
 

Big-name companies joining in

The FDA does not keep a list of approved medical foods or manufacturers. Both small businesses and big food companies like Danone, Nestlé, and Abbott are players. Most products are sold online.

In the United States, Danone’s Nutricia division sells formulas and low-protein foods for IEMs. They also sell Ketocal, a powder or ready-to-drink liquid that is pitched as a balanced medical food to simplify and optimize the ketogenic diet for children with intractable epilepsy. Yet the FDA does not include epilepsy among the conditions that medical foods can treat.

Nestlé sells traditional medical foods for IEMs and also markets a range of what it calls nutritional therapies for such conditions as irritable bowel syndrome and dysphagia.

Nestlé is a minority shareholder in Axona, a product originally developed by Accera (Cerecin as of 2018). Jacquelyn Campo, senior director of global communications at Nestlé Health Sciences, said that the company is not actively involved in the operations management of Cerecin. However, on its website, Nestlé touts Axona, which is only available in the United States, as a “medical food” that “is intended for the clinical dietary management of mild to moderate Alzheimer disease.” The Axona site claims that the main ingredient, caprylic triglyceride, is broken down into ketones that provide fuel to treat cerebral hypometabolism, a precursor to Alzheimer disease. In a 2009 study, daily dosing of a preliminary formulation was associated with improved cognitive performance compared with placebo in patients with mild to moderate Alzheimer disease.

In 2013, the FDA warned Accera that it was misbranding Axona as a medical food and that the therapeutic claims the company was making would make the product an unapproved drug. Ms. Campo said Nestlé is aware of the agency’s warning, but added, “to our knowledge, Cerecin provided answers to the issues raised by the FDA.”

With the goal of getting drug approval, Accera went on to test a tweaked formulation in a 400-patient randomized, placebo-controlled trial called NOURISH AD that ultimately failed. Nevertheless, Axona is still marketed as a medical food. It costs about $100 for a month’s supply.

Repeated requests for comment from Cerecin were not answered. Danielle Schor, an FDA spokesperson, said the agency will not discuss the status of individual products.
 

More disputes and insurance coverage

Mary Ann DeMarco, executive director of sales and marketing for the Scottsdale, Ariz.–based medical food maker Primus Pharmaceuticals, said the company believes its products fit within the FDA’s medical foods rubric.

These include Fosteum Plus capsules, which it markets “for the clinical dietary management of the metabolic processes of osteopenia and osteoporosis.” The capsules contain a combination of genistein, zinc, calcium, phosphate, vitamin K2, and vitamin D. As proof of effectiveness, the company cites clinical data on some of the ingredients – not the product itself.

Primus has run afoul of the FDA before when it similarly positioned another product, called Limbrel, as a medical food for osteoarthritis. From 2007 to 2017, the FDA received 194 adverse event reports associated with Limbrel, including reports of drug-induced liver injury, pancreatitis, and hypersensitivity pneumonitis. In December 2017, the agency urged Primus to recall Limbrel, a move that it said was “necessary to protect the public health and welfare.” Primus withdrew the product but laid out a defense of Limbrel on a devoted website.

The FDA would not comment any further, said Ms. Schor. Ms. DeMarco said that Primus is working with the FDA to bring Limbrel back to market.

A lack of insurance coverage – even for approved medical foods for IEMs – has frustrated advocates, parents, and manufacturers. They are putting their weight behind the Medical Nutrition Equity Act, which would mandate public and private payer coverage of medical foods for IEMs and digestive conditions such as Crohn disease. That 2019 House bill has 56 cosponsors; there is no Senate companion bill.

“If you can get reimbursement, it really makes the market,” for Primus and the other manufacturers, Mr. Hyman said.

Primus Pharmaceuticals has launched its own campaign, Cover My Medical Foods, to enlist consumers and others to the cause.
 

Partnering with advocates

Although its low-protein breads, pastas, and baking products are not considered medical foods by the FDA, Dr. Schär is marketing them as such in the United States. They are trying to make a mark in CKD, according to Ms. Donnelly. She added that Dr. Schär has been successful in Europe, where nutrition therapy is more integrated in the health care system.

In 2019, Flavis and the National Kidney Foundation joined forces to raise awareness of nutritional interventions and to build enthusiasm for the Flavis products. The partnership has now ended, mostly because Flavis could no longer afford it, according to Ms. Donnelly.

“Information on diet and nutrition is the most requested subject matter from the NKF,” said Anthony Gucciardo, senior vice president of strategic partnerships at the foundation. The partnership “has never been necessarily about promoting their products per se; it’s promoting a healthy diet and really a diet specific for CKD.”

The NKF developed cobranded materials on low-protein foods for physicians and a teaching tool they could use with patients. Consumers could access nutrition information and a discount on Flavis products on a dedicated webpage. The foundation didn’t describe the low-protein products as medical foods, said Mr. Gucciardo, even if Flavis promoted them as such.

In patients with CKD, dietary management can help prevent the progression to end-stage renal disease. Although Medicare covers medical nutrition therapy – in which patients receive personalized assessments and dietary advice – uptake is abysmally low, according to a 2018 study.

Dr. Burdock thinks low-protein foods for CKD do meet the FDA’s criteria for a medical food but that the agency might not necessarily agree with him. The FDA would not comment.
 

Physician beware

When it comes to medical foods, the FDA has often looked the other way because the ingredients may already have been proven safe and the danger to an individual or to the public’s health is relatively low, according to Dr. Burdock and Mr. Hyman.

However, if the agency “feels that a medical food will prevent people from seeking medical care or there is potential to defraud the public, it is justified in taking action against the company,” said Dr. Burdock.

According to Dr. Wilson, the pharmacist who reported on the inappropriate medical food prescriptions in the California system, the FDA could help by creating a list of approved medical foods. Physicians should take time to learn about the difference between medical foods and supplements, she said, adding that they should also not hesitate to “question the veracity of the claims for them.”

Ms. Guggenheim believed doctors need to know that, for the most part, these are not FDA-approved products. She emphasized the importance of evaluating the products and looking at the data of their impact on a disease or condition.

“Many of these companies strongly believe that the products work and help people, so clinicians need to be very data driven,” she said.

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

As the Food and Drug Administration focuses on other issues, companies, both big and small, are looking to boost physician and consumer interest in their “medical foods” – products that fall somewhere between drugs and supplements and promise to mitigate symptoms, or even address underlying pathologies, of a range of diseases.

Manufacturers now market an array of medical foods, ranging from powders and capsules for Alzheimer disease to low-protein spaghetti for chronic kidney disease (CKD). The FDA has not been completely absent; it takes a narrow view of what medical conditions qualify for treatment with food products and has warned some manufacturers that their misbranded products are acting more like unapproved drugs.

By the FDA’s definition, medical food is limited to products that provide crucial therapy for patients with inborn errors of metabolism (IEM). An example is specialized baby formula for infants with phenylketonuria. Unlike supplements, medical foods are supposed to be used under the supervision of a physician. This has prompted some sales reps to turn up in the clinic, and most manufacturers have online approval forms for doctors to sign. Manufacturers, advisers, and regulators were interviewed for a closer look at this burgeoning industry.
 

The market

The global market for medical foods – about $18 billion in 2019 – is expected to grow steadily in the near future. It is drawing more interest, especially in Europe, where medical foods are more accepted by physicians and consumers, Meghan Donnelly, MS, RDN, said in an interview. She is a registered dietitian who conducts physician outreach in the United States for Flavis, a division of Dr. Schär. That company, based in northern Italy, started out targeting IEMs but now also sells gluten-free foods for celiac disease and low-protein foods for CKD.

It is still a niche market in the United States – and isn’t likely to ever approach the size of the supplement market, according to Marcus Charuvastra, the managing director of Targeted Medical Pharma, which markets Theramine capsules for pain management, among many other products. But it could still be a big win for a manufacturer if they get a small slice of a big market, such as for Alzheimer disease.
 

Defining medical food

According to an update of the Orphan Drug Act in 1988, a medical food is “a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.” The FDA issued regulations to accompany that law in 1993 but has since only issued a guidance document that is not legally binding.

Medical foods are not drugs and they are not supplements (the latter are intended only for healthy people). The FDA doesn’t require formal approval of a medical food, but, by law, the ingredients must be generally recognized as safe, and manufacturers must follow good manufacturing practices. However, the agency has taken a narrow view of what conditions require medical foods.

Policing medical foods hasn’t been a priority for the FDA, which is why there has been a proliferation of products that don’t meet the FDA’s view of the statutory definition of medical foods, according to Miriam Guggenheim, a food and drug law attorney in Washington, D.C. The FDA usually takes enforcement action when it sees a risk to the public’s health.

The agency’s stance has led to confusion – among manufacturers, physicians, consumers, and even regulators – making the market a kind of Wild West, according to Paul Hyman, a Washington, D.C.–based attorney who has represented medical food companies.

George A. Burdock, PhD, an Orlando-based regulatory consultant who has worked with medical food makers, believes the FDA will be forced to expand their narrow definition. He foresees a reconsideration of many medical food products in light of an October 2019 White House executive order prohibiting federal agencies from issuing guidance in lieu of rules.
 

Manufacturers and the FDA differ

One example of a product about which regulators and manufacturers differ is Theramine, which is described as “specially designed to supply the nervous system with the fuel it needs to meet the altered metabolic requirements of chronic pain and inflammatory disorders.”

It is not considered a medical food by the FDA, and the company has had numerous discussions with the agency about their diverging views, according to Mr. Charuvastra. “We’ve had our warning letters and we’ve had our sit downs, and we just had an inspection.”

Targeted Medical Pharma continues to market its products as medical foods but steers away from making any claims that they are like drugs, he said.

Confusion about medical foods has been exposed in the California Workers’ Compensation System by Leslie Wilson, PhD, and colleagues at the University of California, San Francisco. They found that physicians regularly wrote medical food prescriptions for non–FDA-approved uses and that the system reimbursed the majority of the products at a cost of $15.5 million from 2011 to 2013. More than half of these prescriptions were for Theramine.

Dr. Wilson reported that, for most products, no evidence supported effectiveness, and they were frequently mislabeled – for all 36 that were studied, submissions for reimbursement were made using a National Drug Code, an impossibility because medical foods are not drugs, and 14 were labeled “Rx only.”
 

Big-name companies joining in

The FDA does not keep a list of approved medical foods or manufacturers. Both small businesses and big food companies like Danone, Nestlé, and Abbott are players. Most products are sold online.

In the United States, Danone’s Nutricia division sells formulas and low-protein foods for IEMs. They also sell Ketocal, a powder or ready-to-drink liquid that is pitched as a balanced medical food to simplify and optimize the ketogenic diet for children with intractable epilepsy. Yet the FDA does not include epilepsy among the conditions that medical foods can treat.

Nestlé sells traditional medical foods for IEMs and also markets a range of what it calls nutritional therapies for such conditions as irritable bowel syndrome and dysphagia.

Nestlé is a minority shareholder in Axona, a product originally developed by Accera (Cerecin as of 2018). Jacquelyn Campo, senior director of global communications at Nestlé Health Sciences, said that the company is not actively involved in the operations management of Cerecin. However, on its website, Nestlé touts Axona, which is only available in the United States, as a “medical food” that “is intended for the clinical dietary management of mild to moderate Alzheimer disease.” The Axona site claims that the main ingredient, caprylic triglyceride, is broken down into ketones that provide fuel to treat cerebral hypometabolism, a precursor to Alzheimer disease. In a 2009 study, daily dosing of a preliminary formulation was associated with improved cognitive performance compared with placebo in patients with mild to moderate Alzheimer disease.

In 2013, the FDA warned Accera that it was misbranding Axona as a medical food and that the therapeutic claims the company was making would make the product an unapproved drug. Ms. Campo said Nestlé is aware of the agency’s warning, but added, “to our knowledge, Cerecin provided answers to the issues raised by the FDA.”

With the goal of getting drug approval, Accera went on to test a tweaked formulation in a 400-patient randomized, placebo-controlled trial called NOURISH AD that ultimately failed. Nevertheless, Axona is still marketed as a medical food. It costs about $100 for a month’s supply.

Repeated requests for comment from Cerecin were not answered. Danielle Schor, an FDA spokesperson, said the agency will not discuss the status of individual products.
 

More disputes and insurance coverage

Mary Ann DeMarco, executive director of sales and marketing for the Scottsdale, Ariz.–based medical food maker Primus Pharmaceuticals, said the company believes its products fit within the FDA’s medical foods rubric.

These include Fosteum Plus capsules, which it markets “for the clinical dietary management of the metabolic processes of osteopenia and osteoporosis.” The capsules contain a combination of genistein, zinc, calcium, phosphate, vitamin K2, and vitamin D. As proof of effectiveness, the company cites clinical data on some of the ingredients – not the product itself.

Primus has run afoul of the FDA before when it similarly positioned another product, called Limbrel, as a medical food for osteoarthritis. From 2007 to 2017, the FDA received 194 adverse event reports associated with Limbrel, including reports of drug-induced liver injury, pancreatitis, and hypersensitivity pneumonitis. In December 2017, the agency urged Primus to recall Limbrel, a move that it said was “necessary to protect the public health and welfare.” Primus withdrew the product but laid out a defense of Limbrel on a devoted website.

The FDA would not comment any further, said Ms. Schor. Ms. DeMarco said that Primus is working with the FDA to bring Limbrel back to market.

A lack of insurance coverage – even for approved medical foods for IEMs – has frustrated advocates, parents, and manufacturers. They are putting their weight behind the Medical Nutrition Equity Act, which would mandate public and private payer coverage of medical foods for IEMs and digestive conditions such as Crohn disease. That 2019 House bill has 56 cosponsors; there is no Senate companion bill.

“If you can get reimbursement, it really makes the market,” for Primus and the other manufacturers, Mr. Hyman said.

Primus Pharmaceuticals has launched its own campaign, Cover My Medical Foods, to enlist consumers and others to the cause.
 

Partnering with advocates

Although its low-protein breads, pastas, and baking products are not considered medical foods by the FDA, Dr. Schär is marketing them as such in the United States. They are trying to make a mark in CKD, according to Ms. Donnelly. She added that Dr. Schär has been successful in Europe, where nutrition therapy is more integrated in the health care system.

In 2019, Flavis and the National Kidney Foundation joined forces to raise awareness of nutritional interventions and to build enthusiasm for the Flavis products. The partnership has now ended, mostly because Flavis could no longer afford it, according to Ms. Donnelly.

“Information on diet and nutrition is the most requested subject matter from the NKF,” said Anthony Gucciardo, senior vice president of strategic partnerships at the foundation. The partnership “has never been necessarily about promoting their products per se; it’s promoting a healthy diet and really a diet specific for CKD.”

The NKF developed cobranded materials on low-protein foods for physicians and a teaching tool they could use with patients. Consumers could access nutrition information and a discount on Flavis products on a dedicated webpage. The foundation didn’t describe the low-protein products as medical foods, said Mr. Gucciardo, even if Flavis promoted them as such.

In patients with CKD, dietary management can help prevent the progression to end-stage renal disease. Although Medicare covers medical nutrition therapy – in which patients receive personalized assessments and dietary advice – uptake is abysmally low, according to a 2018 study.

Dr. Burdock thinks low-protein foods for CKD do meet the FDA’s criteria for a medical food but that the agency might not necessarily agree with him. The FDA would not comment.
 

Physician beware

When it comes to medical foods, the FDA has often looked the other way because the ingredients may already have been proven safe and the danger to an individual or to the public’s health is relatively low, according to Dr. Burdock and Mr. Hyman.

However, if the agency “feels that a medical food will prevent people from seeking medical care or there is potential to defraud the public, it is justified in taking action against the company,” said Dr. Burdock.

According to Dr. Wilson, the pharmacist who reported on the inappropriate medical food prescriptions in the California system, the FDA could help by creating a list of approved medical foods. Physicians should take time to learn about the difference between medical foods and supplements, she said, adding that they should also not hesitate to “question the veracity of the claims for them.”

Ms. Guggenheim believed doctors need to know that, for the most part, these are not FDA-approved products. She emphasized the importance of evaluating the products and looking at the data of their impact on a disease or condition.

“Many of these companies strongly believe that the products work and help people, so clinicians need to be very data driven,” she said.

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

As the Food and Drug Administration focuses on other issues, companies, both big and small, are looking to boost physician and consumer interest in their “medical foods” – products that fall somewhere between drugs and supplements and promise to mitigate symptoms, or even address underlying pathologies, of a range of diseases.

Manufacturers now market an array of medical foods, ranging from powders and capsules for Alzheimer disease to low-protein spaghetti for chronic kidney disease (CKD). The FDA has not been completely absent; it takes a narrow view of what medical conditions qualify for treatment with food products and has warned some manufacturers that their misbranded products are acting more like unapproved drugs.

By the FDA’s definition, medical food is limited to products that provide crucial therapy for patients with inborn errors of metabolism (IEM). An example is specialized baby formula for infants with phenylketonuria. Unlike supplements, medical foods are supposed to be used under the supervision of a physician. This has prompted some sales reps to turn up in the clinic, and most manufacturers have online approval forms for doctors to sign. Manufacturers, advisers, and regulators were interviewed for a closer look at this burgeoning industry.
 

The market

The global market for medical foods – about $18 billion in 2019 – is expected to grow steadily in the near future. It is drawing more interest, especially in Europe, where medical foods are more accepted by physicians and consumers, Meghan Donnelly, MS, RDN, said in an interview. She is a registered dietitian who conducts physician outreach in the United States for Flavis, a division of Dr. Schär. That company, based in northern Italy, started out targeting IEMs but now also sells gluten-free foods for celiac disease and low-protein foods for CKD.

It is still a niche market in the United States – and isn’t likely to ever approach the size of the supplement market, according to Marcus Charuvastra, the managing director of Targeted Medical Pharma, which markets Theramine capsules for pain management, among many other products. But it could still be a big win for a manufacturer if they get a small slice of a big market, such as for Alzheimer disease.
 

Defining medical food

According to an update of the Orphan Drug Act in 1988, a medical food is “a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.” The FDA issued regulations to accompany that law in 1993 but has since only issued a guidance document that is not legally binding.

Medical foods are not drugs and they are not supplements (the latter are intended only for healthy people). The FDA doesn’t require formal approval of a medical food, but, by law, the ingredients must be generally recognized as safe, and manufacturers must follow good manufacturing practices. However, the agency has taken a narrow view of what conditions require medical foods.

Policing medical foods hasn’t been a priority for the FDA, which is why there has been a proliferation of products that don’t meet the FDA’s view of the statutory definition of medical foods, according to Miriam Guggenheim, a food and drug law attorney in Washington, D.C. The FDA usually takes enforcement action when it sees a risk to the public’s health.

The agency’s stance has led to confusion – among manufacturers, physicians, consumers, and even regulators – making the market a kind of Wild West, according to Paul Hyman, a Washington, D.C.–based attorney who has represented medical food companies.

George A. Burdock, PhD, an Orlando-based regulatory consultant who has worked with medical food makers, believes the FDA will be forced to expand their narrow definition. He foresees a reconsideration of many medical food products in light of an October 2019 White House executive order prohibiting federal agencies from issuing guidance in lieu of rules.
 

Manufacturers and the FDA differ

One example of a product about which regulators and manufacturers differ is Theramine, which is described as “specially designed to supply the nervous system with the fuel it needs to meet the altered metabolic requirements of chronic pain and inflammatory disorders.”

It is not considered a medical food by the FDA, and the company has had numerous discussions with the agency about their diverging views, according to Mr. Charuvastra. “We’ve had our warning letters and we’ve had our sit downs, and we just had an inspection.”

Targeted Medical Pharma continues to market its products as medical foods but steers away from making any claims that they are like drugs, he said.

Confusion about medical foods has been exposed in the California Workers’ Compensation System by Leslie Wilson, PhD, and colleagues at the University of California, San Francisco. They found that physicians regularly wrote medical food prescriptions for non–FDA-approved uses and that the system reimbursed the majority of the products at a cost of $15.5 million from 2011 to 2013. More than half of these prescriptions were for Theramine.

Dr. Wilson reported that, for most products, no evidence supported effectiveness, and they were frequently mislabeled – for all 36 that were studied, submissions for reimbursement were made using a National Drug Code, an impossibility because medical foods are not drugs, and 14 were labeled “Rx only.”
 

Big-name companies joining in

The FDA does not keep a list of approved medical foods or manufacturers. Both small businesses and big food companies like Danone, Nestlé, and Abbott are players. Most products are sold online.

In the United States, Danone’s Nutricia division sells formulas and low-protein foods for IEMs. They also sell Ketocal, a powder or ready-to-drink liquid that is pitched as a balanced medical food to simplify and optimize the ketogenic diet for children with intractable epilepsy. Yet the FDA does not include epilepsy among the conditions that medical foods can treat.

Nestlé sells traditional medical foods for IEMs and also markets a range of what it calls nutritional therapies for such conditions as irritable bowel syndrome and dysphagia.

Nestlé is a minority shareholder in Axona, a product originally developed by Accera (Cerecin as of 2018). Jacquelyn Campo, senior director of global communications at Nestlé Health Sciences, said that the company is not actively involved in the operations management of Cerecin. However, on its website, Nestlé touts Axona, which is only available in the United States, as a “medical food” that “is intended for the clinical dietary management of mild to moderate Alzheimer disease.” The Axona site claims that the main ingredient, caprylic triglyceride, is broken down into ketones that provide fuel to treat cerebral hypometabolism, a precursor to Alzheimer disease. In a 2009 study, daily dosing of a preliminary formulation was associated with improved cognitive performance compared with placebo in patients with mild to moderate Alzheimer disease.

In 2013, the FDA warned Accera that it was misbranding Axona as a medical food and that the therapeutic claims the company was making would make the product an unapproved drug. Ms. Campo said Nestlé is aware of the agency’s warning, but added, “to our knowledge, Cerecin provided answers to the issues raised by the FDA.”

With the goal of getting drug approval, Accera went on to test a tweaked formulation in a 400-patient randomized, placebo-controlled trial called NOURISH AD that ultimately failed. Nevertheless, Axona is still marketed as a medical food. It costs about $100 for a month’s supply.

Repeated requests for comment from Cerecin were not answered. Danielle Schor, an FDA spokesperson, said the agency will not discuss the status of individual products.
 

More disputes and insurance coverage

Mary Ann DeMarco, executive director of sales and marketing for the Scottsdale, Ariz.–based medical food maker Primus Pharmaceuticals, said the company believes its products fit within the FDA’s medical foods rubric.

These include Fosteum Plus capsules, which it markets “for the clinical dietary management of the metabolic processes of osteopenia and osteoporosis.” The capsules contain a combination of genistein, zinc, calcium, phosphate, vitamin K2, and vitamin D. As proof of effectiveness, the company cites clinical data on some of the ingredients – not the product itself.

Primus has run afoul of the FDA before when it similarly positioned another product, called Limbrel, as a medical food for osteoarthritis. From 2007 to 2017, the FDA received 194 adverse event reports associated with Limbrel, including reports of drug-induced liver injury, pancreatitis, and hypersensitivity pneumonitis. In December 2017, the agency urged Primus to recall Limbrel, a move that it said was “necessary to protect the public health and welfare.” Primus withdrew the product but laid out a defense of Limbrel on a devoted website.

The FDA would not comment any further, said Ms. Schor. Ms. DeMarco said that Primus is working with the FDA to bring Limbrel back to market.

A lack of insurance coverage – even for approved medical foods for IEMs – has frustrated advocates, parents, and manufacturers. They are putting their weight behind the Medical Nutrition Equity Act, which would mandate public and private payer coverage of medical foods for IEMs and digestive conditions such as Crohn disease. That 2019 House bill has 56 cosponsors; there is no Senate companion bill.

“If you can get reimbursement, it really makes the market,” for Primus and the other manufacturers, Mr. Hyman said.

Primus Pharmaceuticals has launched its own campaign, Cover My Medical Foods, to enlist consumers and others to the cause.
 

Partnering with advocates

Although its low-protein breads, pastas, and baking products are not considered medical foods by the FDA, Dr. Schär is marketing them as such in the United States. They are trying to make a mark in CKD, according to Ms. Donnelly. She added that Dr. Schär has been successful in Europe, where nutrition therapy is more integrated in the health care system.

In 2019, Flavis and the National Kidney Foundation joined forces to raise awareness of nutritional interventions and to build enthusiasm for the Flavis products. The partnership has now ended, mostly because Flavis could no longer afford it, according to Ms. Donnelly.

“Information on diet and nutrition is the most requested subject matter from the NKF,” said Anthony Gucciardo, senior vice president of strategic partnerships at the foundation. The partnership “has never been necessarily about promoting their products per se; it’s promoting a healthy diet and really a diet specific for CKD.”

The NKF developed cobranded materials on low-protein foods for physicians and a teaching tool they could use with patients. Consumers could access nutrition information and a discount on Flavis products on a dedicated webpage. The foundation didn’t describe the low-protein products as medical foods, said Mr. Gucciardo, even if Flavis promoted them as such.

In patients with CKD, dietary management can help prevent the progression to end-stage renal disease. Although Medicare covers medical nutrition therapy – in which patients receive personalized assessments and dietary advice – uptake is abysmally low, according to a 2018 study.

Dr. Burdock thinks low-protein foods for CKD do meet the FDA’s criteria for a medical food but that the agency might not necessarily agree with him. The FDA would not comment.
 

Physician beware

When it comes to medical foods, the FDA has often looked the other way because the ingredients may already have been proven safe and the danger to an individual or to the public’s health is relatively low, according to Dr. Burdock and Mr. Hyman.

However, if the agency “feels that a medical food will prevent people from seeking medical care or there is potential to defraud the public, it is justified in taking action against the company,” said Dr. Burdock.

According to Dr. Wilson, the pharmacist who reported on the inappropriate medical food prescriptions in the California system, the FDA could help by creating a list of approved medical foods. Physicians should take time to learn about the difference between medical foods and supplements, she said, adding that they should also not hesitate to “question the veracity of the claims for them.”

Ms. Guggenheim believed doctors need to know that, for the most part, these are not FDA-approved products. She emphasized the importance of evaluating the products and looking at the data of their impact on a disease or condition.

“Many of these companies strongly believe that the products work and help people, so clinicians need to be very data driven,” she said.

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

Less rapid eye movement (REM) sleep is associated with an increased risk for death in middle-aged and older adults, new research suggests.

Investigators at the University of California, San Diego, found that, over a 12-year period, each 5% reduction in REM sleep was associated with a 13% increase in mortality rate. However, the investigators noted that this is only an association and does not indicate cause and effect.

“Determining causality can be difficult,” study investigator Sonia Ancoli-Israel, PhD, professor emeritus of psychiatry at the University of California, San Diego, said in an interview.

“It is therefore important that physicians and the public understand that our findings suggest an increased risk, but that does not mean that reduced REM will always result in shorter survival. With all the self-monitoring sleep gadgets available to the public, I would caution against any panic if one notices reduced REM. But mentioning it to a physician may be a clue to examine what else might be going on with that patient that could more easily be targeted,” Dr. Ancoli-Israel added.

The research was published online July 6 in JAMA Neurology.
 

Negative consequences

Approximately 50-70 million Americans have problems with sleep. Such problems have a multitude of consequences for health, including cardiovascular disease; metabolic, psychiatric, and cognitive disorders; lower quality of life; and increased mortality.

The investigators noted that the aspects of sleep that may be driving this association remain unclear. Because decreased REM sleep has been associated with poor mental and physical health outcomes, the researchers hypothesized that decreased REM sleep may be associated with an increased risk for death.

To test this hypothesis, they conducted a multicenter, population-based, cross-sectional investigation using data from independent cohorts – the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study and the Wisconsin Sleep Cohort (WSC). The MrOS cohort included 2,675 men (mean age, 76.3 years) who were recruited from December 2003 to March 2005 at six U.S. centers and were followed for a median of 12.1 years. The WSC cohort included 1,386 individuals (54.3% men; mean age, 51.5 years) and had a median follow-up of 20.8 years. Data from this study were used to replicate the findings from the MrOS study.

Primary outcome measures included all-cause and cause-specific mortality, which were confirmed using death certificates.

Participants in both cohorts underwent polysomnography and evaluation with the Epworth Sleepiness Scale. For MrOS participants, investigators calculated the total number of minutes per night spent in REM sleep and the corresponding percentage of total sleep time.
 

Less sleep, more death

Self-report sleep measures in MrOS participants were collected using the Pittsburgh Sleep Quality Index and the Functional Outcomes of Sleep Questionnaire

The investigators contacted participants in MrOS every 4 months to determine vital status. Cause of death was categorized by the ICD-9 as cardiovascular, cancer, and other. In WSC, the researchers identified deaths by matching participants’ social security numbers with national and state registries. The cause of death was categorized in the same manner as in the MrOS cohort.

Approximately half (53%) of the MrOS cohort died during follow-up. For each mortality category, the highest percentage of deaths occurred among those in the lowest quartile percentage of REM sleep. Adjusted analyses revealed that the MrOS participants had a 13% higher mortality rate for every 5% reduction in REM sleep (hazard ratio, 1.13; 95% confidence interval, 1.08-1.19). These findings were similar for cardiovascular and other causes of death but were not significant for cancer-related mortality. For all mortality categories, the mortality rate was higher for participants who had less than 15% REM sleep per night in comparison with individuals who had 15% or more.

The findings were similar in the WSC cohort despite its younger age, the inclusion of women, and longer follow-up (HR, 1.13; 95% CI, 1.08-1.19). Compared with MrOS participants, WSC participants were more likely to be obese and to use more antidepressants or sedatives. Overall, the mean percentage of REM sleep was 19.2%. Participants in the lowest quartile of REM sleep generally were older, had higher rates of antidepressant use, hypertension, heart attack, and transient ischemic attack, as well as engaging in less physical activity.
 

Ask about sleep

When the data were stratified by sex, the association between decreased REM sleep and mortality was significant for women but not for men.

“Obtaining a sleep study, representative of the patient’s usual sleep, that shows reduced REM time should alert the neurologist to look for reasons for low REM,” the study’s coinvestigator, Susan Redline, MD, MPH, Peter C. Farrell Professor of Sleep Medicine at Harvard Medical School in Boston, said in an interview.

Dr. Redline added that measures to promote sleep health, such as encouraging regular, sufficient nightly sleep; offering guidance on avoiding alcohol before bedtime and on other healthy sleep practices; and treating sleep disorders may be beneficial.

Low REM time, especially interpreted with other relevant clinical information, may alert the neurologist that a patient may have risk factors for poorer health, she added.

Sleep studies are expensive and are in high demand, so “the most realistic approach is for the neurologist to be asking each and every patient about their sleep,” said Ancoli-Israel.

“By asking a few more questions in every intake, the neurologist is more likely to determine if there are any occult sleep disorders that need to be addressed. By improving sleep in general, one is more likely to also improve any REM abnormalities,” she said.
 

Disease indicator?

In an accompanying editorial, Michael S. Jaffee, MD, vice chair of neurology at the University of Florida in Gainesville, and colleagues noted that the study raises the question of whether REM sleep “could serve as a biomarker for general health.”

“Since the known roles of REM sleep do not easily suggest a causal link with mortality ... it seems more likely that REM sleep reduction is either a crude marker of health or specific disease states that decrease REM sleep may play an important role in contributing to mortality,” they wrote.

Neurologists should remember that certain medications affect sleep architecture, the editorialists advised. They note that serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants reduce REM sleep, and that gabapentin, prazosin, and bupropion, on the other hand, increase REM sleep. However, data regarding whether these medications have an effect on mortality are insufficient.

The editorialists wrote that the study findings are a “welcome addition to the literature and demonstrate definitively that the association between sleep and mortality extends beyond the simple measure of total sleep time.”

Funding for the MrOS and WSC studies was provided by the National Institutes of Health and the National Institute on Aging. Dr. Ancoli-Israel consults for Eisai and Merck on matters unrelated to the study. Dr. Redline has received grants and personal fees from Jazz Pharmaceuticals, consulting fees from Respicardia, and personal fees from Eisai unrelated to the study. Dr. Jaffee served on a data and safety monitoring board for Helius Medical Technologies and consulted for the National Collegiate Athletic Association and the Department of Defense.

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

Less rapid eye movement (REM) sleep is associated with an increased risk for death in middle-aged and older adults, new research suggests.

Investigators at the University of California, San Diego, found that, over a 12-year period, each 5% reduction in REM sleep was associated with a 13% increase in mortality rate. However, the investigators noted that this is only an association and does not indicate cause and effect.

“Determining causality can be difficult,” study investigator Sonia Ancoli-Israel, PhD, professor emeritus of psychiatry at the University of California, San Diego, said in an interview.

“It is therefore important that physicians and the public understand that our findings suggest an increased risk, but that does not mean that reduced REM will always result in shorter survival. With all the self-monitoring sleep gadgets available to the public, I would caution against any panic if one notices reduced REM. But mentioning it to a physician may be a clue to examine what else might be going on with that patient that could more easily be targeted,” Dr. Ancoli-Israel added.

The research was published online July 6 in JAMA Neurology.
 

Negative consequences

Approximately 50-70 million Americans have problems with sleep. Such problems have a multitude of consequences for health, including cardiovascular disease; metabolic, psychiatric, and cognitive disorders; lower quality of life; and increased mortality.

The investigators noted that the aspects of sleep that may be driving this association remain unclear. Because decreased REM sleep has been associated with poor mental and physical health outcomes, the researchers hypothesized that decreased REM sleep may be associated with an increased risk for death.

To test this hypothesis, they conducted a multicenter, population-based, cross-sectional investigation using data from independent cohorts – the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study and the Wisconsin Sleep Cohort (WSC). The MrOS cohort included 2,675 men (mean age, 76.3 years) who were recruited from December 2003 to March 2005 at six U.S. centers and were followed for a median of 12.1 years. The WSC cohort included 1,386 individuals (54.3% men; mean age, 51.5 years) and had a median follow-up of 20.8 years. Data from this study were used to replicate the findings from the MrOS study.

Primary outcome measures included all-cause and cause-specific mortality, which were confirmed using death certificates.

Participants in both cohorts underwent polysomnography and evaluation with the Epworth Sleepiness Scale. For MrOS participants, investigators calculated the total number of minutes per night spent in REM sleep and the corresponding percentage of total sleep time.
 

Less sleep, more death

Self-report sleep measures in MrOS participants were collected using the Pittsburgh Sleep Quality Index and the Functional Outcomes of Sleep Questionnaire

The investigators contacted participants in MrOS every 4 months to determine vital status. Cause of death was categorized by the ICD-9 as cardiovascular, cancer, and other. In WSC, the researchers identified deaths by matching participants’ social security numbers with national and state registries. The cause of death was categorized in the same manner as in the MrOS cohort.

Approximately half (53%) of the MrOS cohort died during follow-up. For each mortality category, the highest percentage of deaths occurred among those in the lowest quartile percentage of REM sleep. Adjusted analyses revealed that the MrOS participants had a 13% higher mortality rate for every 5% reduction in REM sleep (hazard ratio, 1.13; 95% confidence interval, 1.08-1.19). These findings were similar for cardiovascular and other causes of death but were not significant for cancer-related mortality. For all mortality categories, the mortality rate was higher for participants who had less than 15% REM sleep per night in comparison with individuals who had 15% or more.

The findings were similar in the WSC cohort despite its younger age, the inclusion of women, and longer follow-up (HR, 1.13; 95% CI, 1.08-1.19). Compared with MrOS participants, WSC participants were more likely to be obese and to use more antidepressants or sedatives. Overall, the mean percentage of REM sleep was 19.2%. Participants in the lowest quartile of REM sleep generally were older, had higher rates of antidepressant use, hypertension, heart attack, and transient ischemic attack, as well as engaging in less physical activity.
 

Ask about sleep

When the data were stratified by sex, the association between decreased REM sleep and mortality was significant for women but not for men.

“Obtaining a sleep study, representative of the patient’s usual sleep, that shows reduced REM time should alert the neurologist to look for reasons for low REM,” the study’s coinvestigator, Susan Redline, MD, MPH, Peter C. Farrell Professor of Sleep Medicine at Harvard Medical School in Boston, said in an interview.

Dr. Redline added that measures to promote sleep health, such as encouraging regular, sufficient nightly sleep; offering guidance on avoiding alcohol before bedtime and on other healthy sleep practices; and treating sleep disorders may be beneficial.

Low REM time, especially interpreted with other relevant clinical information, may alert the neurologist that a patient may have risk factors for poorer health, she added.

Sleep studies are expensive and are in high demand, so “the most realistic approach is for the neurologist to be asking each and every patient about their sleep,” said Ancoli-Israel.

“By asking a few more questions in every intake, the neurologist is more likely to determine if there are any occult sleep disorders that need to be addressed. By improving sleep in general, one is more likely to also improve any REM abnormalities,” she said.
 

Disease indicator?

In an accompanying editorial, Michael S. Jaffee, MD, vice chair of neurology at the University of Florida in Gainesville, and colleagues noted that the study raises the question of whether REM sleep “could serve as a biomarker for general health.”

“Since the known roles of REM sleep do not easily suggest a causal link with mortality ... it seems more likely that REM sleep reduction is either a crude marker of health or specific disease states that decrease REM sleep may play an important role in contributing to mortality,” they wrote.

Neurologists should remember that certain medications affect sleep architecture, the editorialists advised. They note that serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants reduce REM sleep, and that gabapentin, prazosin, and bupropion, on the other hand, increase REM sleep. However, data regarding whether these medications have an effect on mortality are insufficient.

The editorialists wrote that the study findings are a “welcome addition to the literature and demonstrate definitively that the association between sleep and mortality extends beyond the simple measure of total sleep time.”

Funding for the MrOS and WSC studies was provided by the National Institutes of Health and the National Institute on Aging. Dr. Ancoli-Israel consults for Eisai and Merck on matters unrelated to the study. Dr. Redline has received grants and personal fees from Jazz Pharmaceuticals, consulting fees from Respicardia, and personal fees from Eisai unrelated to the study. Dr. Jaffee served on a data and safety monitoring board for Helius Medical Technologies and consulted for the National Collegiate Athletic Association and the Department of Defense.

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

Less rapid eye movement (REM) sleep is associated with an increased risk for death in middle-aged and older adults, new research suggests.

Investigators at the University of California, San Diego, found that, over a 12-year period, each 5% reduction in REM sleep was associated with a 13% increase in mortality rate. However, the investigators noted that this is only an association and does not indicate cause and effect.

“Determining causality can be difficult,” study investigator Sonia Ancoli-Israel, PhD, professor emeritus of psychiatry at the University of California, San Diego, said in an interview.

“It is therefore important that physicians and the public understand that our findings suggest an increased risk, but that does not mean that reduced REM will always result in shorter survival. With all the self-monitoring sleep gadgets available to the public, I would caution against any panic if one notices reduced REM. But mentioning it to a physician may be a clue to examine what else might be going on with that patient that could more easily be targeted,” Dr. Ancoli-Israel added.

The research was published online July 6 in JAMA Neurology.
 

Negative consequences

Approximately 50-70 million Americans have problems with sleep. Such problems have a multitude of consequences for health, including cardiovascular disease; metabolic, psychiatric, and cognitive disorders; lower quality of life; and increased mortality.

The investigators noted that the aspects of sleep that may be driving this association remain unclear. Because decreased REM sleep has been associated with poor mental and physical health outcomes, the researchers hypothesized that decreased REM sleep may be associated with an increased risk for death.

To test this hypothesis, they conducted a multicenter, population-based, cross-sectional investigation using data from independent cohorts – the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study and the Wisconsin Sleep Cohort (WSC). The MrOS cohort included 2,675 men (mean age, 76.3 years) who were recruited from December 2003 to March 2005 at six U.S. centers and were followed for a median of 12.1 years. The WSC cohort included 1,386 individuals (54.3% men; mean age, 51.5 years) and had a median follow-up of 20.8 years. Data from this study were used to replicate the findings from the MrOS study.

Primary outcome measures included all-cause and cause-specific mortality, which were confirmed using death certificates.

Participants in both cohorts underwent polysomnography and evaluation with the Epworth Sleepiness Scale. For MrOS participants, investigators calculated the total number of minutes per night spent in REM sleep and the corresponding percentage of total sleep time.
 

Less sleep, more death

Self-report sleep measures in MrOS participants were collected using the Pittsburgh Sleep Quality Index and the Functional Outcomes of Sleep Questionnaire

The investigators contacted participants in MrOS every 4 months to determine vital status. Cause of death was categorized by the ICD-9 as cardiovascular, cancer, and other. In WSC, the researchers identified deaths by matching participants’ social security numbers with national and state registries. The cause of death was categorized in the same manner as in the MrOS cohort.

Approximately half (53%) of the MrOS cohort died during follow-up. For each mortality category, the highest percentage of deaths occurred among those in the lowest quartile percentage of REM sleep. Adjusted analyses revealed that the MrOS participants had a 13% higher mortality rate for every 5% reduction in REM sleep (hazard ratio, 1.13; 95% confidence interval, 1.08-1.19). These findings were similar for cardiovascular and other causes of death but were not significant for cancer-related mortality. For all mortality categories, the mortality rate was higher for participants who had less than 15% REM sleep per night in comparison with individuals who had 15% or more.

The findings were similar in the WSC cohort despite its younger age, the inclusion of women, and longer follow-up (HR, 1.13; 95% CI, 1.08-1.19). Compared with MrOS participants, WSC participants were more likely to be obese and to use more antidepressants or sedatives. Overall, the mean percentage of REM sleep was 19.2%. Participants in the lowest quartile of REM sleep generally were older, had higher rates of antidepressant use, hypertension, heart attack, and transient ischemic attack, as well as engaging in less physical activity.
 

Ask about sleep

When the data were stratified by sex, the association between decreased REM sleep and mortality was significant for women but not for men.

“Obtaining a sleep study, representative of the patient’s usual sleep, that shows reduced REM time should alert the neurologist to look for reasons for low REM,” the study’s coinvestigator, Susan Redline, MD, MPH, Peter C. Farrell Professor of Sleep Medicine at Harvard Medical School in Boston, said in an interview.

Dr. Redline added that measures to promote sleep health, such as encouraging regular, sufficient nightly sleep; offering guidance on avoiding alcohol before bedtime and on other healthy sleep practices; and treating sleep disorders may be beneficial.

Low REM time, especially interpreted with other relevant clinical information, may alert the neurologist that a patient may have risk factors for poorer health, she added.

Sleep studies are expensive and are in high demand, so “the most realistic approach is for the neurologist to be asking each and every patient about their sleep,” said Ancoli-Israel.

“By asking a few more questions in every intake, the neurologist is more likely to determine if there are any occult sleep disorders that need to be addressed. By improving sleep in general, one is more likely to also improve any REM abnormalities,” she said.
 

Disease indicator?

In an accompanying editorial, Michael S. Jaffee, MD, vice chair of neurology at the University of Florida in Gainesville, and colleagues noted that the study raises the question of whether REM sleep “could serve as a biomarker for general health.”

“Since the known roles of REM sleep do not easily suggest a causal link with mortality ... it seems more likely that REM sleep reduction is either a crude marker of health or specific disease states that decrease REM sleep may play an important role in contributing to mortality,” they wrote.

Neurologists should remember that certain medications affect sleep architecture, the editorialists advised. They note that serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants reduce REM sleep, and that gabapentin, prazosin, and bupropion, on the other hand, increase REM sleep. However, data regarding whether these medications have an effect on mortality are insufficient.

The editorialists wrote that the study findings are a “welcome addition to the literature and demonstrate definitively that the association between sleep and mortality extends beyond the simple measure of total sleep time.”

Funding for the MrOS and WSC studies was provided by the National Institutes of Health and the National Institute on Aging. Dr. Ancoli-Israel consults for Eisai and Merck on matters unrelated to the study. Dr. Redline has received grants and personal fees from Jazz Pharmaceuticals, consulting fees from Respicardia, and personal fees from Eisai unrelated to the study. Dr. Jaffee served on a data and safety monitoring board for Helius Medical Technologies and consulted for the National Collegiate Athletic Association and the Department of Defense.

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

Concentrations of neurofilament light (NfL) chain in blood can detect concussion, its severity and help predict recovery in patients with mild traumatic brain injury (TBI), new research indicates.

“Blood NfL may be used to aid in the diagnosis of patients with concussion or mild TBI [and] to identify individuals at increased risk of developing persistent postconcussive symptoms following TBI,” said lead author Pashtun Shahim, MD, PhD, National Institutes of Health Clinical Center, Bethesda, Md.

“This study is the first to do a detailed assessment of serum NfL chain and advanced brain imaging in multiple cohorts, brain injury severities, and time points after injury. The cohorts included professional athletes and nonathletes, and over time up to 5 years after TBI,” Dr. Shahim added.

The study was published online July 8 in Neurology.
 

Rapid indicator of neuronal damage

The researchers studied two cohorts of patients with head injuries. In the first, they determined serum and CSF NfL chain levels in professional Swedish ice hockey players (median age, 27 years), including 45 with acute concussion, 31 with repetitive concussions and persistent post-concussive symptoms (PCS), 28 who contributed samples during preseason with no recent concussion, and 14 healthy nonathletes.

CSF and serum NfL concentrations were closely correlated (r = 0.71; P < .0001). Serum NfL distinguished players with persistent PCS due to repetitive concussions from preseason concussion-free players, with an area under the receiver operating characteristic curve of 0.97. Higher CSF and serum NfL levels were associated with a higher number of concussions and severity of PCS after 1 year.

The second cohort involved 230 clinic-based adults (mean age, 43 years), including 162 with TBI and 68 healthy controls. In this cohort, patients with TBI had increased serum NfL concentrations compared with controls for up to 5 years, and these concentrations were able to distinguish between mild, moderate, and severe TBI. Serum NfL also correlated with measures of functional outcome, MRI brain atrophy, and diffusion tensor imaging estimates of traumatic axonal injury.

“Our findings suggest that NfL concentrations in serum offer rapid and accessible means of assessing and predicting neuronal damage in patients with TBI,” the investigators wrote.

What’s needed going forward, said Dr. Shahim, is “validation in larger cohorts for determining what levels of NfL in blood may be associated with a specific type of TBI, and what the levels are in healthy individuals of different ages.”

Not ready for prime time

In an accompanying editorial, Christopher Filley, MD, University of Colorado at Denver, Aurora, noted that NfL “may prove useful in identifying TBI patients at risk for prolonged symptoms and in enabling more focused treatment for these individuals.”

“These reports are richly laden with acute and longitudinal data that not only support the use of NfL as a convenient diagnostic test for TBI, but plausibly correlate with the neuropathology of TBI that is thought to play a major role in immediate and lasting cognitive disability,” he wrote.

Although the origin of TBI-induced cognitive decline is not entirely explained by traumatic axonal injury, “NfL appears to have much promise as a blood test that relates directly to the ubiquitous white matter damage of TBI, revealing a great deal about not only whether a TBI occurred, but also the extent of injury sustained, and how this injury may affect patient outcome for years thereafter,” Dr. Filley wrote.

However, he cautioned more research is needed before the blood test can be routinely applied to TBI diagnosis in clinical practice. “Among the hurdles still ahead are the standardization of measurement techniques across analytical platforms, and the determination of precise cutoffs between normal and abnormal values in different ages groups and at varying levels of TBI severity,” Dr. Filley noted.

The research was supported by the National Institutes of Health, the Department of Defense, the Center for Neuroscience and Regenerative Medicine at the Uniformed Services University, and the Swedish Research Council. Dr. Shahim and Dr. Filley have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Concentrations of neurofilament light (NfL) chain in blood can detect concussion, its severity and help predict recovery in patients with mild traumatic brain injury (TBI), new research indicates.

“Blood NfL may be used to aid in the diagnosis of patients with concussion or mild TBI [and] to identify individuals at increased risk of developing persistent postconcussive symptoms following TBI,” said lead author Pashtun Shahim, MD, PhD, National Institutes of Health Clinical Center, Bethesda, Md.

“This study is the first to do a detailed assessment of serum NfL chain and advanced brain imaging in multiple cohorts, brain injury severities, and time points after injury. The cohorts included professional athletes and nonathletes, and over time up to 5 years after TBI,” Dr. Shahim added.

The study was published online July 8 in Neurology.
 

Rapid indicator of neuronal damage

The researchers studied two cohorts of patients with head injuries. In the first, they determined serum and CSF NfL chain levels in professional Swedish ice hockey players (median age, 27 years), including 45 with acute concussion, 31 with repetitive concussions and persistent post-concussive symptoms (PCS), 28 who contributed samples during preseason with no recent concussion, and 14 healthy nonathletes.

CSF and serum NfL concentrations were closely correlated (r = 0.71; P < .0001). Serum NfL distinguished players with persistent PCS due to repetitive concussions from preseason concussion-free players, with an area under the receiver operating characteristic curve of 0.97. Higher CSF and serum NfL levels were associated with a higher number of concussions and severity of PCS after 1 year.

The second cohort involved 230 clinic-based adults (mean age, 43 years), including 162 with TBI and 68 healthy controls. In this cohort, patients with TBI had increased serum NfL concentrations compared with controls for up to 5 years, and these concentrations were able to distinguish between mild, moderate, and severe TBI. Serum NfL also correlated with measures of functional outcome, MRI brain atrophy, and diffusion tensor imaging estimates of traumatic axonal injury.

“Our findings suggest that NfL concentrations in serum offer rapid and accessible means of assessing and predicting neuronal damage in patients with TBI,” the investigators wrote.

What’s needed going forward, said Dr. Shahim, is “validation in larger cohorts for determining what levels of NfL in blood may be associated with a specific type of TBI, and what the levels are in healthy individuals of different ages.”

Not ready for prime time

In an accompanying editorial, Christopher Filley, MD, University of Colorado at Denver, Aurora, noted that NfL “may prove useful in identifying TBI patients at risk for prolonged symptoms and in enabling more focused treatment for these individuals.”

“These reports are richly laden with acute and longitudinal data that not only support the use of NfL as a convenient diagnostic test for TBI, but plausibly correlate with the neuropathology of TBI that is thought to play a major role in immediate and lasting cognitive disability,” he wrote.

Although the origin of TBI-induced cognitive decline is not entirely explained by traumatic axonal injury, “NfL appears to have much promise as a blood test that relates directly to the ubiquitous white matter damage of TBI, revealing a great deal about not only whether a TBI occurred, but also the extent of injury sustained, and how this injury may affect patient outcome for years thereafter,” Dr. Filley wrote.

However, he cautioned more research is needed before the blood test can be routinely applied to TBI diagnosis in clinical practice. “Among the hurdles still ahead are the standardization of measurement techniques across analytical platforms, and the determination of precise cutoffs between normal and abnormal values in different ages groups and at varying levels of TBI severity,” Dr. Filley noted.

The research was supported by the National Institutes of Health, the Department of Defense, the Center for Neuroscience and Regenerative Medicine at the Uniformed Services University, and the Swedish Research Council. Dr. Shahim and Dr. Filley have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Concentrations of neurofilament light (NfL) chain in blood can detect concussion, its severity and help predict recovery in patients with mild traumatic brain injury (TBI), new research indicates.

“Blood NfL may be used to aid in the diagnosis of patients with concussion or mild TBI [and] to identify individuals at increased risk of developing persistent postconcussive symptoms following TBI,” said lead author Pashtun Shahim, MD, PhD, National Institutes of Health Clinical Center, Bethesda, Md.

“This study is the first to do a detailed assessment of serum NfL chain and advanced brain imaging in multiple cohorts, brain injury severities, and time points after injury. The cohorts included professional athletes and nonathletes, and over time up to 5 years after TBI,” Dr. Shahim added.

The study was published online July 8 in Neurology.
 

Rapid indicator of neuronal damage

The researchers studied two cohorts of patients with head injuries. In the first, they determined serum and CSF NfL chain levels in professional Swedish ice hockey players (median age, 27 years), including 45 with acute concussion, 31 with repetitive concussions and persistent post-concussive symptoms (PCS), 28 who contributed samples during preseason with no recent concussion, and 14 healthy nonathletes.

CSF and serum NfL concentrations were closely correlated (r = 0.71; P < .0001). Serum NfL distinguished players with persistent PCS due to repetitive concussions from preseason concussion-free players, with an area under the receiver operating characteristic curve of 0.97. Higher CSF and serum NfL levels were associated with a higher number of concussions and severity of PCS after 1 year.

The second cohort involved 230 clinic-based adults (mean age, 43 years), including 162 with TBI and 68 healthy controls. In this cohort, patients with TBI had increased serum NfL concentrations compared with controls for up to 5 years, and these concentrations were able to distinguish between mild, moderate, and severe TBI. Serum NfL also correlated with measures of functional outcome, MRI brain atrophy, and diffusion tensor imaging estimates of traumatic axonal injury.

“Our findings suggest that NfL concentrations in serum offer rapid and accessible means of assessing and predicting neuronal damage in patients with TBI,” the investigators wrote.

What’s needed going forward, said Dr. Shahim, is “validation in larger cohorts for determining what levels of NfL in blood may be associated with a specific type of TBI, and what the levels are in healthy individuals of different ages.”

Not ready for prime time

In an accompanying editorial, Christopher Filley, MD, University of Colorado at Denver, Aurora, noted that NfL “may prove useful in identifying TBI patients at risk for prolonged symptoms and in enabling more focused treatment for these individuals.”

“These reports are richly laden with acute and longitudinal data that not only support the use of NfL as a convenient diagnostic test for TBI, but plausibly correlate with the neuropathology of TBI that is thought to play a major role in immediate and lasting cognitive disability,” he wrote.

Although the origin of TBI-induced cognitive decline is not entirely explained by traumatic axonal injury, “NfL appears to have much promise as a blood test that relates directly to the ubiquitous white matter damage of TBI, revealing a great deal about not only whether a TBI occurred, but also the extent of injury sustained, and how this injury may affect patient outcome for years thereafter,” Dr. Filley wrote.

However, he cautioned more research is needed before the blood test can be routinely applied to TBI diagnosis in clinical practice. “Among the hurdles still ahead are the standardization of measurement techniques across analytical platforms, and the determination of precise cutoffs between normal and abnormal values in different ages groups and at varying levels of TBI severity,” Dr. Filley noted.

The research was supported by the National Institutes of Health, the Department of Defense, the Center for Neuroscience and Regenerative Medicine at the Uniformed Services University, and the Swedish Research Council. Dr. Shahim and Dr. Filley have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Ten patients smiled and waved out on the computer monitor, as Jacob Mirsky, MD, greeted each one, asked them to introduce themselves, and inquired as to how each was doing with their stress reduction tactics.

The attendees of the online session had been patients at in-person group visits at the Massachusetts General Hospital Revere HealthCare Center. But those in-person group sessions, known as shared medical appointments (SMAs), were shut down when COVID-19 arrived.

“Our group patients have been missing the sessions,” said Dr. Mirsky, a general internist who codirects the center’s group visit program. The online sessions, called virtual SMAs (V-SMAs), work well with COVID-19 social distancing.

In the group sessions, Dr. Mirsky reads a standardized message that addresses privacy concerns during the session. For the next 60-90 minutes, “we ask them to talk about what has gone well for them and what they are struggling with,” he said. “Then I answer their questions using materials in a PowerPoint to address key points, such as reducing salt for high blood pressure or interpreting blood sugar levels for diabetes.

“I try to end group sessions with one area of focus,” Dr. Mirsky said. “In the stress reduction group, this could be meditation. In the diabetes group, it could be a discussion on weight loss.” Then the program’s health coach goes over some key concepts on behavior change and invites participants to contact her after the session.

“The nice thing is that these virtual sessions are fully reimbursable by all of our insurers in Massachusetts,” Dr. Mirsky said. Through evaluation and management (E/M) codes, each patient in a group visit is paid the same as a patient in an individual visit with the same level of complexity.

Dr. Mirsky writes a note in the chart about each patient who was in the group session. “This includes information about the specific patient, such as the history and physical, and information about the group meeting,” he said. In the next few months, the center plans to put its other group sessions online – on blood pressure, obesity, diabetes, and insomnia.

Attracting doctors who hadn’t done groups before

The COVID-19 crisis has given group visits a second wind. Some doctors who never used SMAs before are now trying out this new mode of patient engagement, said Marianne Sumego, MD, director of the Cleveland Clinic’s SMA program, which began 21 years ago.

In this era of COVID-19, group visits have either switched to V-SMAs or halted. However, the COVID-19 crisis has given group visits a second wind. Some doctors who never used SMAs before are now trying out this new mode of patient engagement,

Many of the 100 doctors using SMAs at the Cleveland Clinic have switched over to V-SMAs for now, and the new mode is also attracting colleagues who are new to SMAs, she said.

“When doctors started using telemedicine, virtual group visits started making sense to them,” Dr. Sumego said. “This is a time of a great deal of experimentation in practice design.”

Indeed, V-SMAs have eliminated some problems that had discouraged doctors from trying SMAs, said Amy Wheeler, MD, a general internist who founded the Revere SMA program and codirects it with Dr. Mirsky.

V-SMAs eliminate the need for a large space to hold sessions and reduce the number of staff needed to run sessions, Dr. Wheeler said. “Virtual group visits can actually be easier to use than in-person group visits.”

Dr. Sumego believes small practices in particular will take up V-SMAs because they are easier to run than regular SMAs. “Necessity drives change,” she said. “Across the country everyone is looking at the virtual group model.”

Group visits can help your bottom line

Medicare and many private payers cover group visits. In most cases, they tend to pay the same rate as for an individual office visit. As with telehealth, Medicare and many other payers are temporarily reimbursing for virtual visits at the same rate as for real visits.

Not all payers have a stated policy about covering SMAs, and physicians have to ask. The Centers for Medicare & Medicaid Services, for example, has not published any coding rules on SMAs. But in response to a query by the American Academy of Family Physicians, CMS said it would allow use of CPT codes for E/M services for individual patients.

Blue Cross Blue Shield of North Carolina is one of the few payers with a clearly stated policy on its website. Like Medicare, the insurer accepts E/M codes, and it requires that patients’ attendance must be voluntary; they must be established patients; and the visit must be specific to a disease or condition, although several conditions are allowed.

Dr. Mirsky said his group uses the same E/M level – 99213 – for all of his SMA patients. “Since a regular primary care visit is usually billed at a level 3 or 4, depending on how many topics are covered, we chose level 3 for groups, because the group session deals with just one topic.”

One challenge for billing for SMAs is that most health insurers require patients to provide a copay for each visit, which can discourage patients in groups that meet frequently, says Wayne Dysinger, MD, founder of Lifestyle Medical Solutions, a two-physician primary care practice in Riverside, Calif.

But Dr. Dysinger, who has been using SMAs for 5 years, usually doesn’t have to worry about copays because much of his work is capitated and doesn’t require a copay.

Also, some of Dr. Dysinger’s SMA patients are in direct primary care, in which the patients pay an $18 monthly membership fee. Other practices may charge a flat out-of-pocket fee.
 

How group visits operate

SMAs are based on the observation that patients with the same condition generally ask their doctor the same questions, and rather than repeat the answers each time, why not provide them to a group?

Dr. Wheeler said trying to be more efficient with her time was the primary reason she became interested in SMAs a dozen years ago. “I was trying to squeeze the advice patients needed into a normal patient visit, and it wasn’t working. When I tried to tell them everything they needed to know, I’d run behind for the rest of my day’s visits.”

She found she was continually repeating the same conversation with patients, but these talks weren’t detailed enough to be effective. “When my weight loss patients came back for the next appointment, they had not made the recommended changes in lifestyle. I started to realize how complicated weight loss was.” So Dr. Wheeler founded the SMA program at the Revere Center.

Doctors enjoy the patient interaction

Some doctors who use SMAs talk about how connected they feel with their patients. “For me, the group sessions are the most gratifying part of the week,” Dr. Dysinger says. “I like to see the patients interacting with me and with each other, and watch their health behavior change over time.”

“These groups have a great deal of energy,” he said. “They have a kind of vulnerability that is very raw, very human. People make commitments to meet goals. Will they meet them or not?”

Dr. Dysinger’s enthusiasm has been echoed by other doctors. In a study of older patients, physicians who used SMAs were more satisfied with care than physicians who relied on standard one-to-one interactions. In another study, the researchers surmised that, in SMAs, doctors learn from their patients how they can better meet their needs.

Dr. Dysinger thinks SMAs are widely applicable in primary care. He estimates that 80%-85% of appointments at a primary care practice involve chronic diseases, and this type of patient is a good fit for group visits. SMAs typically treat patients with diabetes, asthma, arthritis, and obesity.

Dr. Sumego said SMAs are used for specialty care at Cleveland Clinic, such as to help patients before and after bariatric surgery. SMAs have also been used to treat patients with ulcerative colitis, multiple sclerosis, cancer, HIV, menopause, insomnia, and stress, according to one report.

Dr. Dysinger, who runs a small practice, organizes his group sessions somewhat differently. He doesn’t organize his groups around conditions like diabetes, but instead his groups focus on four “pillars” of lifestyle medicine: nourishment, movement, resilience (involving sleep and stress), and connectedness.
 

Why patients like group visits

Feeling part of a whole is a major draw for many patients. “Patients seem to like committing to something bigger than just themselves,” Dr. Wheeler said. “They enjoy the sense of community that groups have, the joy of supporting one another.”

“It’s feeling that you’re not alone,” Dr. Mirsky said. “When a patient struggling with diabetes hears how hard it is for another patient, it validates their experience and gives them someone to connect with. There is a positive peer pressure.”

Many programs, including Dr. Wheeler’s and Dr. Mirsky’s in Boston, allow patients to drop in and out of sessions, rather than attending one course all the way through. But even under this format, Dr. Wheeler said that patients often tend to stick together. “At the end of a session, one patient asks another: ‘Which session do you want to go to next?’ ” she said.

Patients also learn from each other in SMAs. Patients exchange experiences and share advice they may not have had the chance to get during an individual visit.

The group dynamic can make it easier for some patients to reveal sensitive information, said Dr. Dysinger. “In these groups, people feel free to talk about their bowel movements, or about having to deal with the influence of a parent on their lives,” Dr. Dysinger said. “The sessions can have the feel of an [Alcoholics Anonymous] meeting, but they’re firmly grounded in medicine.”

Potential downsides of virtual group visits

SMAs and VSMAs may not work for every practice. Some small practices may not have enough patients to organize a group visit around a particular condition – even a common one like diabetes. In a presentation before the Society of General Internal Medicine, a physician from the Medical University of South Carolina, Charleston, warned that it may be difficult for a practice to fill diabetes group visits every year.

Additionally, some patients don’t want to talk about personal matters in a group. “They may not want to reveal certain things about themselves,” Dr. Mirsky said. “So I tell the group that if there is anything that anyone wants to talk about in private, I’m available.”

Another drawback of SMAs is that more experienced patients may have to slog through information they already know, which is a particular problem when patients can drop in and out of sessions. Dr. Mirsky noted that “what often ends up happening is that the experienced participant helps the newcomer.”

Finally, confidentially is a big concern in a group session. “In a one-on-one visit, you can go into details about the patient’s health, and even bring up an entry in the chart,” Dr. Wheeler said. “But in a group visit, you can’t raise any personal details about a patient unless the patient brings it up first.”

SMA patients sign confidentiality agreements in which they agree not to talk about other patients outside the session. Ensuring confidentiality becomes more complicated in virtual group visits, because someone located in the room near a participant could overhear the conversation. For this reason, patients in V-SMAs are advised to use headphones or, at a minimum, close the door to the room they are in.

To address privacy concerns, Zoom encrypts its data, but some privacy breeches have been reported, and a U.S. senator has been looking into Zoom’s privacy vulnerabilities.

Transferring groups to virtual groups

It took the COVID-19 crisis for most doctors to take up virtual SMAs. Dr. Sumego said that the Cleveland Clinic started virtual SMAs more than a year ago, but most other groups operating SMAs were apparently not providing them virtually before COVID-19 started.

Dr. Dysinger said he tried virtual SMAs in 2017 but dropped them because the technology – using Zoom – was challenging at the time, and his staff and most patients were resistant. “Only three to five people were attending the virtual sessions, and the meetings took place in the evening, which was hard on the staff.”

“When COVID-19 first appeared, our initial response was to try to keep the in-person group and add social distancing to it, but that wasn’t workable, so very quickly we shifted to Zoom meetings,” Dr. Dysinger said. “We had experience with Zoom already, and the Zoom technology had improved and was easier to use. COVID-19 forced it all forward.”

Are V-SMAs effective? While there have been many studies showing the effectiveness of in-person SMAs, there have been very few on V-SMAs. One 2018 study of obesity patients found that those attending in-person SMAs lost somewhat more weight than those in V-SMAs.

As with telemedicine, some patients have trouble with the technology of V-SMAs. Dr. Dysinger said 5%-10% of his SMA patients don’t make the switch over to V-SMAs – mainly because of problems in adapting to the technology – but the rest are happy. “We’re averaging 10 people per meeting, and as many as 20.”

Getting comfortable with group visits

Dealing with group visits takes a very different mindset than what doctors normally have, Dr. Wheeler said. “It took me 6-8 months to feel comfortable enough with group sessions to do them myself,” she recalled. “This was a very different way to practice, compared to the one-on-one care I was trained to give patients. Others may find the transition easier, though.

“Doctors are used to being in control of the patient visit, but the exchange in a group visit is more fluid,” Dr. Wheeler said. “Patients offer their own opinions, and this sends the discussion off on a tangent that is often quite useful. As doctors, we have to learn when to let these tangents continue, and know when the discussion might have to be brought back to the theme at hand. Often it’s better not to intercede.”

Do doctors need training to conduct SMAs? Patients in group visits reported worse communication with physicians than those in individual visits, according to a 2014 study. The authors surmised that the doctors needed to learn how to talk to groups and suggested that they get some training.

The potential staying power of V-SMAs post COVID?

Once the COVID-19 crisis is over, Medicare is scheduled to no longer provide the same level of reimbursement for virtual sessions as for real sessions. Dr. Mirsky anticipates a great deal of resistance to this change from thousands of physicians and patients who have become comfortable with telehealth, including virtual SMAs.

Dr. Dysinger thinks V-SMAs will continue. “When COVID-19 clears and we can go back to in-person groups, we expect to keep some virtual groups. People have already come to accept and value virtual groups.”

Dr. Wheeler sees virtual groups playing an essential role post COVID-19, when practices have to get back up to speed. “Virtual group visits could make it easier to deal with a large backlog of patients who couldn’t be seen up until now,” she said. “And virtual groups will be the only way to see patients who are still reluctant to meet in a group.”

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

Ten patients smiled and waved out on the computer monitor, as Jacob Mirsky, MD, greeted each one, asked them to introduce themselves, and inquired as to how each was doing with their stress reduction tactics.

The attendees of the online session had been patients at in-person group visits at the Massachusetts General Hospital Revere HealthCare Center. But those in-person group sessions, known as shared medical appointments (SMAs), were shut down when COVID-19 arrived.

“Our group patients have been missing the sessions,” said Dr. Mirsky, a general internist who codirects the center’s group visit program. The online sessions, called virtual SMAs (V-SMAs), work well with COVID-19 social distancing.

In the group sessions, Dr. Mirsky reads a standardized message that addresses privacy concerns during the session. For the next 60-90 minutes, “we ask them to talk about what has gone well for them and what they are struggling with,” he said. “Then I answer their questions using materials in a PowerPoint to address key points, such as reducing salt for high blood pressure or interpreting blood sugar levels for diabetes.

“I try to end group sessions with one area of focus,” Dr. Mirsky said. “In the stress reduction group, this could be meditation. In the diabetes group, it could be a discussion on weight loss.” Then the program’s health coach goes over some key concepts on behavior change and invites participants to contact her after the session.

“The nice thing is that these virtual sessions are fully reimbursable by all of our insurers in Massachusetts,” Dr. Mirsky said. Through evaluation and management (E/M) codes, each patient in a group visit is paid the same as a patient in an individual visit with the same level of complexity.

Dr. Mirsky writes a note in the chart about each patient who was in the group session. “This includes information about the specific patient, such as the history and physical, and information about the group meeting,” he said. In the next few months, the center plans to put its other group sessions online – on blood pressure, obesity, diabetes, and insomnia.

Attracting doctors who hadn’t done groups before

The COVID-19 crisis has given group visits a second wind. Some doctors who never used SMAs before are now trying out this new mode of patient engagement, said Marianne Sumego, MD, director of the Cleveland Clinic’s SMA program, which began 21 years ago.

In this era of COVID-19, group visits have either switched to V-SMAs or halted. However, the COVID-19 crisis has given group visits a second wind. Some doctors who never used SMAs before are now trying out this new mode of patient engagement,

Many of the 100 doctors using SMAs at the Cleveland Clinic have switched over to V-SMAs for now, and the new mode is also attracting colleagues who are new to SMAs, she said.

“When doctors started using telemedicine, virtual group visits started making sense to them,” Dr. Sumego said. “This is a time of a great deal of experimentation in practice design.”

Indeed, V-SMAs have eliminated some problems that had discouraged doctors from trying SMAs, said Amy Wheeler, MD, a general internist who founded the Revere SMA program and codirects it with Dr. Mirsky.

V-SMAs eliminate the need for a large space to hold sessions and reduce the number of staff needed to run sessions, Dr. Wheeler said. “Virtual group visits can actually be easier to use than in-person group visits.”

Dr. Sumego believes small practices in particular will take up V-SMAs because they are easier to run than regular SMAs. “Necessity drives change,” she said. “Across the country everyone is looking at the virtual group model.”

Group visits can help your bottom line

Medicare and many private payers cover group visits. In most cases, they tend to pay the same rate as for an individual office visit. As with telehealth, Medicare and many other payers are temporarily reimbursing for virtual visits at the same rate as for real visits.

Not all payers have a stated policy about covering SMAs, and physicians have to ask. The Centers for Medicare & Medicaid Services, for example, has not published any coding rules on SMAs. But in response to a query by the American Academy of Family Physicians, CMS said it would allow use of CPT codes for E/M services for individual patients.

Blue Cross Blue Shield of North Carolina is one of the few payers with a clearly stated policy on its website. Like Medicare, the insurer accepts E/M codes, and it requires that patients’ attendance must be voluntary; they must be established patients; and the visit must be specific to a disease or condition, although several conditions are allowed.

Dr. Mirsky said his group uses the same E/M level – 99213 – for all of his SMA patients. “Since a regular primary care visit is usually billed at a level 3 or 4, depending on how many topics are covered, we chose level 3 for groups, because the group session deals with just one topic.”

One challenge for billing for SMAs is that most health insurers require patients to provide a copay for each visit, which can discourage patients in groups that meet frequently, says Wayne Dysinger, MD, founder of Lifestyle Medical Solutions, a two-physician primary care practice in Riverside, Calif.

But Dr. Dysinger, who has been using SMAs for 5 years, usually doesn’t have to worry about copays because much of his work is capitated and doesn’t require a copay.

Also, some of Dr. Dysinger’s SMA patients are in direct primary care, in which the patients pay an $18 monthly membership fee. Other practices may charge a flat out-of-pocket fee.
 

How group visits operate

SMAs are based on the observation that patients with the same condition generally ask their doctor the same questions, and rather than repeat the answers each time, why not provide them to a group?

Dr. Wheeler said trying to be more efficient with her time was the primary reason she became interested in SMAs a dozen years ago. “I was trying to squeeze the advice patients needed into a normal patient visit, and it wasn’t working. When I tried to tell them everything they needed to know, I’d run behind for the rest of my day’s visits.”

She found she was continually repeating the same conversation with patients, but these talks weren’t detailed enough to be effective. “When my weight loss patients came back for the next appointment, they had not made the recommended changes in lifestyle. I started to realize how complicated weight loss was.” So Dr. Wheeler founded the SMA program at the Revere Center.

Doctors enjoy the patient interaction

Some doctors who use SMAs talk about how connected they feel with their patients. “For me, the group sessions are the most gratifying part of the week,” Dr. Dysinger says. “I like to see the patients interacting with me and with each other, and watch their health behavior change over time.”

“These groups have a great deal of energy,” he said. “They have a kind of vulnerability that is very raw, very human. People make commitments to meet goals. Will they meet them or not?”

Dr. Dysinger’s enthusiasm has been echoed by other doctors. In a study of older patients, physicians who used SMAs were more satisfied with care than physicians who relied on standard one-to-one interactions. In another study, the researchers surmised that, in SMAs, doctors learn from their patients how they can better meet their needs.

Dr. Dysinger thinks SMAs are widely applicable in primary care. He estimates that 80%-85% of appointments at a primary care practice involve chronic diseases, and this type of patient is a good fit for group visits. SMAs typically treat patients with diabetes, asthma, arthritis, and obesity.

Dr. Sumego said SMAs are used for specialty care at Cleveland Clinic, such as to help patients before and after bariatric surgery. SMAs have also been used to treat patients with ulcerative colitis, multiple sclerosis, cancer, HIV, menopause, insomnia, and stress, according to one report.

Dr. Dysinger, who runs a small practice, organizes his group sessions somewhat differently. He doesn’t organize his groups around conditions like diabetes, but instead his groups focus on four “pillars” of lifestyle medicine: nourishment, movement, resilience (involving sleep and stress), and connectedness.
 

Why patients like group visits

Feeling part of a whole is a major draw for many patients. “Patients seem to like committing to something bigger than just themselves,” Dr. Wheeler said. “They enjoy the sense of community that groups have, the joy of supporting one another.”

“It’s feeling that you’re not alone,” Dr. Mirsky said. “When a patient struggling with diabetes hears how hard it is for another patient, it validates their experience and gives them someone to connect with. There is a positive peer pressure.”

Many programs, including Dr. Wheeler’s and Dr. Mirsky’s in Boston, allow patients to drop in and out of sessions, rather than attending one course all the way through. But even under this format, Dr. Wheeler said that patients often tend to stick together. “At the end of a session, one patient asks another: ‘Which session do you want to go to next?’ ” she said.

Patients also learn from each other in SMAs. Patients exchange experiences and share advice they may not have had the chance to get during an individual visit.

The group dynamic can make it easier for some patients to reveal sensitive information, said Dr. Dysinger. “In these groups, people feel free to talk about their bowel movements, or about having to deal with the influence of a parent on their lives,” Dr. Dysinger said. “The sessions can have the feel of an [Alcoholics Anonymous] meeting, but they’re firmly grounded in medicine.”

Potential downsides of virtual group visits

SMAs and VSMAs may not work for every practice. Some small practices may not have enough patients to organize a group visit around a particular condition – even a common one like diabetes. In a presentation before the Society of General Internal Medicine, a physician from the Medical University of South Carolina, Charleston, warned that it may be difficult for a practice to fill diabetes group visits every year.

Additionally, some patients don’t want to talk about personal matters in a group. “They may not want to reveal certain things about themselves,” Dr. Mirsky said. “So I tell the group that if there is anything that anyone wants to talk about in private, I’m available.”

Another drawback of SMAs is that more experienced patients may have to slog through information they already know, which is a particular problem when patients can drop in and out of sessions. Dr. Mirsky noted that “what often ends up happening is that the experienced participant helps the newcomer.”

Finally, confidentially is a big concern in a group session. “In a one-on-one visit, you can go into details about the patient’s health, and even bring up an entry in the chart,” Dr. Wheeler said. “But in a group visit, you can’t raise any personal details about a patient unless the patient brings it up first.”

SMA patients sign confidentiality agreements in which they agree not to talk about other patients outside the session. Ensuring confidentiality becomes more complicated in virtual group visits, because someone located in the room near a participant could overhear the conversation. For this reason, patients in V-SMAs are advised to use headphones or, at a minimum, close the door to the room they are in.

To address privacy concerns, Zoom encrypts its data, but some privacy breeches have been reported, and a U.S. senator has been looking into Zoom’s privacy vulnerabilities.

Transferring groups to virtual groups

It took the COVID-19 crisis for most doctors to take up virtual SMAs. Dr. Sumego said that the Cleveland Clinic started virtual SMAs more than a year ago, but most other groups operating SMAs were apparently not providing them virtually before COVID-19 started.

Dr. Dysinger said he tried virtual SMAs in 2017 but dropped them because the technology – using Zoom – was challenging at the time, and his staff and most patients were resistant. “Only three to five people were attending the virtual sessions, and the meetings took place in the evening, which was hard on the staff.”

“When COVID-19 first appeared, our initial response was to try to keep the in-person group and add social distancing to it, but that wasn’t workable, so very quickly we shifted to Zoom meetings,” Dr. Dysinger said. “We had experience with Zoom already, and the Zoom technology had improved and was easier to use. COVID-19 forced it all forward.”

Are V-SMAs effective? While there have been many studies showing the effectiveness of in-person SMAs, there have been very few on V-SMAs. One 2018 study of obesity patients found that those attending in-person SMAs lost somewhat more weight than those in V-SMAs.

As with telemedicine, some patients have trouble with the technology of V-SMAs. Dr. Dysinger said 5%-10% of his SMA patients don’t make the switch over to V-SMAs – mainly because of problems in adapting to the technology – but the rest are happy. “We’re averaging 10 people per meeting, and as many as 20.”

Getting comfortable with group visits

Dealing with group visits takes a very different mindset than what doctors normally have, Dr. Wheeler said. “It took me 6-8 months to feel comfortable enough with group sessions to do them myself,” she recalled. “This was a very different way to practice, compared to the one-on-one care I was trained to give patients. Others may find the transition easier, though.

“Doctors are used to being in control of the patient visit, but the exchange in a group visit is more fluid,” Dr. Wheeler said. “Patients offer their own opinions, and this sends the discussion off on a tangent that is often quite useful. As doctors, we have to learn when to let these tangents continue, and know when the discussion might have to be brought back to the theme at hand. Often it’s better not to intercede.”

Do doctors need training to conduct SMAs? Patients in group visits reported worse communication with physicians than those in individual visits, according to a 2014 study. The authors surmised that the doctors needed to learn how to talk to groups and suggested that they get some training.

The potential staying power of V-SMAs post COVID?

Once the COVID-19 crisis is over, Medicare is scheduled to no longer provide the same level of reimbursement for virtual sessions as for real sessions. Dr. Mirsky anticipates a great deal of resistance to this change from thousands of physicians and patients who have become comfortable with telehealth, including virtual SMAs.

Dr. Dysinger thinks V-SMAs will continue. “When COVID-19 clears and we can go back to in-person groups, we expect to keep some virtual groups. People have already come to accept and value virtual groups.”

Dr. Wheeler sees virtual groups playing an essential role post COVID-19, when practices have to get back up to speed. “Virtual group visits could make it easier to deal with a large backlog of patients who couldn’t be seen up until now,” she said. “And virtual groups will be the only way to see patients who are still reluctant to meet in a group.”

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

Ten patients smiled and waved out on the computer monitor, as Jacob Mirsky, MD, greeted each one, asked them to introduce themselves, and inquired as to how each was doing with their stress reduction tactics.

The attendees of the online session had been patients at in-person group visits at the Massachusetts General Hospital Revere HealthCare Center. But those in-person group sessions, known as shared medical appointments (SMAs), were shut down when COVID-19 arrived.

“Our group patients have been missing the sessions,” said Dr. Mirsky, a general internist who codirects the center’s group visit program. The online sessions, called virtual SMAs (V-SMAs), work well with COVID-19 social distancing.

In the group sessions, Dr. Mirsky reads a standardized message that addresses privacy concerns during the session. For the next 60-90 minutes, “we ask them to talk about what has gone well for them and what they are struggling with,” he said. “Then I answer their questions using materials in a PowerPoint to address key points, such as reducing salt for high blood pressure or interpreting blood sugar levels for diabetes.

“I try to end group sessions with one area of focus,” Dr. Mirsky said. “In the stress reduction group, this could be meditation. In the diabetes group, it could be a discussion on weight loss.” Then the program’s health coach goes over some key concepts on behavior change and invites participants to contact her after the session.

“The nice thing is that these virtual sessions are fully reimbursable by all of our insurers in Massachusetts,” Dr. Mirsky said. Through evaluation and management (E/M) codes, each patient in a group visit is paid the same as a patient in an individual visit with the same level of complexity.

Dr. Mirsky writes a note in the chart about each patient who was in the group session. “This includes information about the specific patient, such as the history and physical, and information about the group meeting,” he said. In the next few months, the center plans to put its other group sessions online – on blood pressure, obesity, diabetes, and insomnia.

Attracting doctors who hadn’t done groups before

The COVID-19 crisis has given group visits a second wind. Some doctors who never used SMAs before are now trying out this new mode of patient engagement, said Marianne Sumego, MD, director of the Cleveland Clinic’s SMA program, which began 21 years ago.

In this era of COVID-19, group visits have either switched to V-SMAs or halted. However, the COVID-19 crisis has given group visits a second wind. Some doctors who never used SMAs before are now trying out this new mode of patient engagement,

Many of the 100 doctors using SMAs at the Cleveland Clinic have switched over to V-SMAs for now, and the new mode is also attracting colleagues who are new to SMAs, she said.

“When doctors started using telemedicine, virtual group visits started making sense to them,” Dr. Sumego said. “This is a time of a great deal of experimentation in practice design.”

Indeed, V-SMAs have eliminated some problems that had discouraged doctors from trying SMAs, said Amy Wheeler, MD, a general internist who founded the Revere SMA program and codirects it with Dr. Mirsky.

V-SMAs eliminate the need for a large space to hold sessions and reduce the number of staff needed to run sessions, Dr. Wheeler said. “Virtual group visits can actually be easier to use than in-person group visits.”

Dr. Sumego believes small practices in particular will take up V-SMAs because they are easier to run than regular SMAs. “Necessity drives change,” she said. “Across the country everyone is looking at the virtual group model.”

Group visits can help your bottom line

Medicare and many private payers cover group visits. In most cases, they tend to pay the same rate as for an individual office visit. As with telehealth, Medicare and many other payers are temporarily reimbursing for virtual visits at the same rate as for real visits.

Not all payers have a stated policy about covering SMAs, and physicians have to ask. The Centers for Medicare & Medicaid Services, for example, has not published any coding rules on SMAs. But in response to a query by the American Academy of Family Physicians, CMS said it would allow use of CPT codes for E/M services for individual patients.

Blue Cross Blue Shield of North Carolina is one of the few payers with a clearly stated policy on its website. Like Medicare, the insurer accepts E/M codes, and it requires that patients’ attendance must be voluntary; they must be established patients; and the visit must be specific to a disease or condition, although several conditions are allowed.

Dr. Mirsky said his group uses the same E/M level – 99213 – for all of his SMA patients. “Since a regular primary care visit is usually billed at a level 3 or 4, depending on how many topics are covered, we chose level 3 for groups, because the group session deals with just one topic.”

One challenge for billing for SMAs is that most health insurers require patients to provide a copay for each visit, which can discourage patients in groups that meet frequently, says Wayne Dysinger, MD, founder of Lifestyle Medical Solutions, a two-physician primary care practice in Riverside, Calif.

But Dr. Dysinger, who has been using SMAs for 5 years, usually doesn’t have to worry about copays because much of his work is capitated and doesn’t require a copay.

Also, some of Dr. Dysinger’s SMA patients are in direct primary care, in which the patients pay an $18 monthly membership fee. Other practices may charge a flat out-of-pocket fee.
 

How group visits operate

SMAs are based on the observation that patients with the same condition generally ask their doctor the same questions, and rather than repeat the answers each time, why not provide them to a group?

Dr. Wheeler said trying to be more efficient with her time was the primary reason she became interested in SMAs a dozen years ago. “I was trying to squeeze the advice patients needed into a normal patient visit, and it wasn’t working. When I tried to tell them everything they needed to know, I’d run behind for the rest of my day’s visits.”

She found she was continually repeating the same conversation with patients, but these talks weren’t detailed enough to be effective. “When my weight loss patients came back for the next appointment, they had not made the recommended changes in lifestyle. I started to realize how complicated weight loss was.” So Dr. Wheeler founded the SMA program at the Revere Center.

Doctors enjoy the patient interaction

Some doctors who use SMAs talk about how connected they feel with their patients. “For me, the group sessions are the most gratifying part of the week,” Dr. Dysinger says. “I like to see the patients interacting with me and with each other, and watch their health behavior change over time.”

“These groups have a great deal of energy,” he said. “They have a kind of vulnerability that is very raw, very human. People make commitments to meet goals. Will they meet them or not?”

Dr. Dysinger’s enthusiasm has been echoed by other doctors. In a study of older patients, physicians who used SMAs were more satisfied with care than physicians who relied on standard one-to-one interactions. In another study, the researchers surmised that, in SMAs, doctors learn from their patients how they can better meet their needs.

Dr. Dysinger thinks SMAs are widely applicable in primary care. He estimates that 80%-85% of appointments at a primary care practice involve chronic diseases, and this type of patient is a good fit for group visits. SMAs typically treat patients with diabetes, asthma, arthritis, and obesity.

Dr. Sumego said SMAs are used for specialty care at Cleveland Clinic, such as to help patients before and after bariatric surgery. SMAs have also been used to treat patients with ulcerative colitis, multiple sclerosis, cancer, HIV, menopause, insomnia, and stress, according to one report.

Dr. Dysinger, who runs a small practice, organizes his group sessions somewhat differently. He doesn’t organize his groups around conditions like diabetes, but instead his groups focus on four “pillars” of lifestyle medicine: nourishment, movement, resilience (involving sleep and stress), and connectedness.
 

Why patients like group visits

Feeling part of a whole is a major draw for many patients. “Patients seem to like committing to something bigger than just themselves,” Dr. Wheeler said. “They enjoy the sense of community that groups have, the joy of supporting one another.”

“It’s feeling that you’re not alone,” Dr. Mirsky said. “When a patient struggling with diabetes hears how hard it is for another patient, it validates their experience and gives them someone to connect with. There is a positive peer pressure.”

Many programs, including Dr. Wheeler’s and Dr. Mirsky’s in Boston, allow patients to drop in and out of sessions, rather than attending one course all the way through. But even under this format, Dr. Wheeler said that patients often tend to stick together. “At the end of a session, one patient asks another: ‘Which session do you want to go to next?’ ” she said.

Patients also learn from each other in SMAs. Patients exchange experiences and share advice they may not have had the chance to get during an individual visit.

The group dynamic can make it easier for some patients to reveal sensitive information, said Dr. Dysinger. “In these groups, people feel free to talk about their bowel movements, or about having to deal with the influence of a parent on their lives,” Dr. Dysinger said. “The sessions can have the feel of an [Alcoholics Anonymous] meeting, but they’re firmly grounded in medicine.”

Potential downsides of virtual group visits

SMAs and VSMAs may not work for every practice. Some small practices may not have enough patients to organize a group visit around a particular condition – even a common one like diabetes. In a presentation before the Society of General Internal Medicine, a physician from the Medical University of South Carolina, Charleston, warned that it may be difficult for a practice to fill diabetes group visits every year.

Additionally, some patients don’t want to talk about personal matters in a group. “They may not want to reveal certain things about themselves,” Dr. Mirsky said. “So I tell the group that if there is anything that anyone wants to talk about in private, I’m available.”

Another drawback of SMAs is that more experienced patients may have to slog through information they already know, which is a particular problem when patients can drop in and out of sessions. Dr. Mirsky noted that “what often ends up happening is that the experienced participant helps the newcomer.”

Finally, confidentially is a big concern in a group session. “In a one-on-one visit, you can go into details about the patient’s health, and even bring up an entry in the chart,” Dr. Wheeler said. “But in a group visit, you can’t raise any personal details about a patient unless the patient brings it up first.”

SMA patients sign confidentiality agreements in which they agree not to talk about other patients outside the session. Ensuring confidentiality becomes more complicated in virtual group visits, because someone located in the room near a participant could overhear the conversation. For this reason, patients in V-SMAs are advised to use headphones or, at a minimum, close the door to the room they are in.

To address privacy concerns, Zoom encrypts its data, but some privacy breeches have been reported, and a U.S. senator has been looking into Zoom’s privacy vulnerabilities.

Transferring groups to virtual groups

It took the COVID-19 crisis for most doctors to take up virtual SMAs. Dr. Sumego said that the Cleveland Clinic started virtual SMAs more than a year ago, but most other groups operating SMAs were apparently not providing them virtually before COVID-19 started.

Dr. Dysinger said he tried virtual SMAs in 2017 but dropped them because the technology – using Zoom – was challenging at the time, and his staff and most patients were resistant. “Only three to five people were attending the virtual sessions, and the meetings took place in the evening, which was hard on the staff.”

“When COVID-19 first appeared, our initial response was to try to keep the in-person group and add social distancing to it, but that wasn’t workable, so very quickly we shifted to Zoom meetings,” Dr. Dysinger said. “We had experience with Zoom already, and the Zoom technology had improved and was easier to use. COVID-19 forced it all forward.”

Are V-SMAs effective? While there have been many studies showing the effectiveness of in-person SMAs, there have been very few on V-SMAs. One 2018 study of obesity patients found that those attending in-person SMAs lost somewhat more weight than those in V-SMAs.

As with telemedicine, some patients have trouble with the technology of V-SMAs. Dr. Dysinger said 5%-10% of his SMA patients don’t make the switch over to V-SMAs – mainly because of problems in adapting to the technology – but the rest are happy. “We’re averaging 10 people per meeting, and as many as 20.”

Getting comfortable with group visits

Dealing with group visits takes a very different mindset than what doctors normally have, Dr. Wheeler said. “It took me 6-8 months to feel comfortable enough with group sessions to do them myself,” she recalled. “This was a very different way to practice, compared to the one-on-one care I was trained to give patients. Others may find the transition easier, though.

“Doctors are used to being in control of the patient visit, but the exchange in a group visit is more fluid,” Dr. Wheeler said. “Patients offer their own opinions, and this sends the discussion off on a tangent that is often quite useful. As doctors, we have to learn when to let these tangents continue, and know when the discussion might have to be brought back to the theme at hand. Often it’s better not to intercede.”

Do doctors need training to conduct SMAs? Patients in group visits reported worse communication with physicians than those in individual visits, according to a 2014 study. The authors surmised that the doctors needed to learn how to talk to groups and suggested that they get some training.

The potential staying power of V-SMAs post COVID?

Once the COVID-19 crisis is over, Medicare is scheduled to no longer provide the same level of reimbursement for virtual sessions as for real sessions. Dr. Mirsky anticipates a great deal of resistance to this change from thousands of physicians and patients who have become comfortable with telehealth, including virtual SMAs.

Dr. Dysinger thinks V-SMAs will continue. “When COVID-19 clears and we can go back to in-person groups, we expect to keep some virtual groups. People have already come to accept and value virtual groups.”

Dr. Wheeler sees virtual groups playing an essential role post COVID-19, when practices have to get back up to speed. “Virtual group visits could make it easier to deal with a large backlog of patients who couldn’t be seen up until now,” she said. “And virtual groups will be the only way to see patients who are still reluctant to meet in a group.”

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

Hopefully 2020 will be the strangest year in modern memory, but who knows?

Things continue to be surreal at my office. I haven’t seen my staff since mid-March, even though I’m in touch with them all day long. Fortunately we live in an age where many things can be handled from home.

At the office I’d started to see an increase in patients, but that has dropped off again as the infection rate in Arizona has soared out of control. I’m not complaining about patients staying home; many neurology patients are frail or on immune-suppressing agents, and should not be out and about.

Normally I’m a stickler for stable patients coming in once a year for refills, but in 2020 I’m letting that slide. Sumatriptan, levetiracetam, and nortriptyline are better filled for 90 days to minimize potential COVID-19 contacts on all parts – including mine.

Originally I thought that some degree of normalcy would be back by August, but clearly that won’t be the case. Arizona, and many other states, continue to get worse as political ambitions trounce sound science.

A year ago I routinely fielded calls asking whether various supplements would fend off Alzheimer’s disease as the manufacturers claimed (NO! THEY DON’T!). Today similar calls come in asking about stuff marketed to prevent and cure COVID-19 (same answer).

I have no idea when this will improve. My kids are scheduled to move back into their dorms in about a month, but realistically I don’t see that safely happening. Classrooms, with the reduced capacity needed and cost of frequent cleanings, seem impractical, compared with Zoom.

The college football season is almost certainly going to be canceled. The NFL maybe. Basketball and baseball are playing out reduced seasons in sterilized bubbles. Sports, next to holidays and school, are the cyclical touchstones our society is measured by. Their disruption reflects the strangeness of the year as a whole.

As always during the Phoenix summer, I’m hiding in an air-conditioned office, waiting for patients to come in. It’s quieter without my secretary and her energetic 4-year-old daughter. But I’m still here. It’s strange with the unfamiliar silence, but the routine of coming to work each day, even on a reduced schedule, brings a sense of normalcy. There may not be as many patients, but those who need me come in, and as long as I’m able to, I’ll be here to help them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Hopefully 2020 will be the strangest year in modern memory, but who knows?

Things continue to be surreal at my office. I haven’t seen my staff since mid-March, even though I’m in touch with them all day long. Fortunately we live in an age where many things can be handled from home.

At the office I’d started to see an increase in patients, but that has dropped off again as the infection rate in Arizona has soared out of control. I’m not complaining about patients staying home; many neurology patients are frail or on immune-suppressing agents, and should not be out and about.

Normally I’m a stickler for stable patients coming in once a year for refills, but in 2020 I’m letting that slide. Sumatriptan, levetiracetam, and nortriptyline are better filled for 90 days to minimize potential COVID-19 contacts on all parts – including mine.

Originally I thought that some degree of normalcy would be back by August, but clearly that won’t be the case. Arizona, and many other states, continue to get worse as political ambitions trounce sound science.

A year ago I routinely fielded calls asking whether various supplements would fend off Alzheimer’s disease as the manufacturers claimed (NO! THEY DON’T!). Today similar calls come in asking about stuff marketed to prevent and cure COVID-19 (same answer).

I have no idea when this will improve. My kids are scheduled to move back into their dorms in about a month, but realistically I don’t see that safely happening. Classrooms, with the reduced capacity needed and cost of frequent cleanings, seem impractical, compared with Zoom.

The college football season is almost certainly going to be canceled. The NFL maybe. Basketball and baseball are playing out reduced seasons in sterilized bubbles. Sports, next to holidays and school, are the cyclical touchstones our society is measured by. Their disruption reflects the strangeness of the year as a whole.

As always during the Phoenix summer, I’m hiding in an air-conditioned office, waiting for patients to come in. It’s quieter without my secretary and her energetic 4-year-old daughter. But I’m still here. It’s strange with the unfamiliar silence, but the routine of coming to work each day, even on a reduced schedule, brings a sense of normalcy. There may not be as many patients, but those who need me come in, and as long as I’m able to, I’ll be here to help them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Hopefully 2020 will be the strangest year in modern memory, but who knows?

Things continue to be surreal at my office. I haven’t seen my staff since mid-March, even though I’m in touch with them all day long. Fortunately we live in an age where many things can be handled from home.

At the office I’d started to see an increase in patients, but that has dropped off again as the infection rate in Arizona has soared out of control. I’m not complaining about patients staying home; many neurology patients are frail or on immune-suppressing agents, and should not be out and about.

Normally I’m a stickler for stable patients coming in once a year for refills, but in 2020 I’m letting that slide. Sumatriptan, levetiracetam, and nortriptyline are better filled for 90 days to minimize potential COVID-19 contacts on all parts – including mine.

Originally I thought that some degree of normalcy would be back by August, but clearly that won’t be the case. Arizona, and many other states, continue to get worse as political ambitions trounce sound science.

A year ago I routinely fielded calls asking whether various supplements would fend off Alzheimer’s disease as the manufacturers claimed (NO! THEY DON’T!). Today similar calls come in asking about stuff marketed to prevent and cure COVID-19 (same answer).

I have no idea when this will improve. My kids are scheduled to move back into their dorms in about a month, but realistically I don’t see that safely happening. Classrooms, with the reduced capacity needed and cost of frequent cleanings, seem impractical, compared with Zoom.

The college football season is almost certainly going to be canceled. The NFL maybe. Basketball and baseball are playing out reduced seasons in sterilized bubbles. Sports, next to holidays and school, are the cyclical touchstones our society is measured by. Their disruption reflects the strangeness of the year as a whole.

As always during the Phoenix summer, I’m hiding in an air-conditioned office, waiting for patients to come in. It’s quieter without my secretary and her energetic 4-year-old daughter. But I’m still here. It’s strange with the unfamiliar silence, but the routine of coming to work each day, even on a reduced schedule, brings a sense of normalcy. There may not be as many patients, but those who need me come in, and as long as I’m able to, I’ll be here to help them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Two early studies are raising hopes that some genetic forms of amyotrophic lateral sclerosis (ALS) can be treated. Both studies investigated potential benefits of suppressing the toxic activity in cells of a mutant gene (SOD1) that encodes superoxide dismutase 1 (SOD1) in patients with ALS.

One study investigated the antisense oligonucleotide (ASO) tofersen (Biogen); the other study examined viral vector–mediated gene suppression.

The studies’ promising results signal “the beginning of a new precision medicine–based approach towards treating ALS,” said Orla Hardiman, BSc, MB, BCh, BAO, MD, a consultant neurologist and professor of neurology at Trinity College and Beaumont Hospital in Dublin, Ireland. Dr. Hardiman co-authored an editorial that accompanied the two studies, which were published July 9 in the New England Journal of Medicine.
 

Genetic culprits

ALS is a disorder of progressive degeneration of upper and lower motor neurons. It typically leads to death from ventilatory failure within 5 years of symptom onset.

Genetic factors are responsible for about half the risk variance of ALS. In populations of European origin, variants in SOD1 account for an estimated 13% to 20% of familial ALS, although this rate varies around the world. Although SOD1 is not the most common variant in ALS, it is the one that researchers are most familiar with and has been studied in an animal model.

In the first study, investigators evaluated the safety, pharmacokinetics, and pharmacodynamics of the ASO tofersen in adults with ALS.

An ASO is a small piece of nucleic acid that enters neurons in the spinal cord and brain, explained co-investigator Toby A. Ferguson, MD, PhD, vice president and head of the neuromuscular development unit at Biogen.

ASO binds to the SOD1 gene and knocks down the SOD1 protein, which is the “toxic engine [that] drives the disease, kills neurons, and causes patients to have loss of function and eventually to die,” said Dr. Ferguson. “The ASO turns off the motor that produces that toxic protein,” he added.

Animal studies have shown that ASOs that target SOD1 messenger RNA transcripts prolong survival, improve motor performance, and reduce SOD1 protein concentrations.

The new phase 1/2 double-blind study included 50 adults at 18 sites in the United States, Canada, and four European countries. All had muscle weakness attributed to ALS and a documented SOD1 mutation. Participants were randomly assigned to receive one of four doses of tofersen—20, 40, 60, or 100 mg—or placebo. Treatment was administered via a lumbar intrathecal bolus injection. The study included a screening period followed by a 12-week intervention period and a 12-week follow-up.
 

Adverse events

A primary outcome was the incidence of adverse events (AEs) and serious AEs. Results showed that all participants reported one or more AEs. The most common AEs were headache, pain at the injection site, post–lumbar puncture syndrome, and falls. Three deaths occurred, one in the placebo group, one in the 20-mg dose group, and one in the 60-mg dose group. There were no serious AEs in the 100-mg group.

Although the investigators found an increase in cerebrospinal fluid (CSF) protein and white cell counts, there was no clear association between these observations and higher doses of tofersen or longer duration of exposure.

“We don’t know the implications of this, and it’s something we need to keep an eye on as we move these studies forward,” Dr. Ferguson said.

None of the AEs or CSF abnormalities led to trial discontinuation.

A secondary outcome was change in SOD1 protein concentration in CSF at day 85. The study showed that SOD1 concentrations decreased by 36% among the participants who received tofersen 100 mg and by lesser amounts in the patients who received lower doses. Concentrations in the placebo group were reduced by 3%.

The 36% reduction in the highest dose group is likely meaningful and “foundational to the concept of what this molecule can do,” Dr. Ferguson said.

“If the number one cause of SOD1 ALS is accumulation of toxic SOD1 protein, then the demonstration that we can reduce SOD1 protein in the CSF ... is saying that’s the first step on the way to showing the molecule is doing what it should do,” he added.
 

Emerging tool

In patients with ALS, neurofilament concentrations typically increase as the disease progresses. However, this study documented a reduction in these CSF concentrations. “One interpretation of that could be that there is less neurodegeneration or neuro injury” in patients treated with tofersen, Dr. Ferguson said.

He noted that neurofilament is “an emerging tool” for understanding neurodegeneration. It could also “be another sort of biochemical signal that the molecule is doing something important,” he added.

However, he noted that neurofilament concentration is still an exploratory marker.

Exploratory analyses suggested a possible slowing of functional loss, as measured by the ALS Functional Rating Scale–Revised (ALSFRS-R) score and the handheld dynamometry megascore. The latter assesses strength in 16 muscle groups in the arms and legs. The investigators noted that no conclusions can be drawn from these outcomes.

A post hoc analysis showed that among patients with SOD1 mutations associated with a fast-progressing disease course, the slope of clinical decline might have been gentler, and there was a greater decrease in CSF neurofilament concentration compared among those whose disease followed a slower course.

This suggests that “if you pick the right target,” even patients with severe disease can be treated, Dr. Ferguson said.

He acknowledged that in a relatively short study such as this one, it may be easier to see benefits in patients whose disease is progressing rapidly. However, he’s convinced that the treatment “would work for all SOD1 ALS patients, not just fast patients.”

Dr. Ferguson said the study investigators are encouraged by the new data, which “really suggest that we may be developing a meaningful treatment for SOD1 ALS.” However, “it’s still early” in terms of rolling out this therapy for patients with ALS, he said.

The safety and efficacy of tofersen are currently being evaluated in a phase 3, randomized, double-blind, placebo-controlled trial.

Limitations of the current study were the small number of participants, the short duration of treatment and follow-up, the exploratory nature of efficacy outcomes, and the post hoc methods for defining the fast-progressing subgroup.

Although an advantage of tofersen is that it can enter the nucleus of the cell, perhaps boosting effectiveness, a drawback might be that patients need several treatments administered via lumbar puncture. Following three initial doses, the drug is given every month.

An alternative approach might be a viral vector approach.
 

“Stunning” finding

In the second study, investigators assessed the safety of a single intrathecal infusion of a viral vector therapy designed to target SOD1 in two patients with familial ALS. The two patients were a 22-year-old man whose mother had died of ALS at age 45 and a 56-year-old man who had a family history of ALS.

The aim of the viral vector therapy is to continually suppress mutant gene activity, said study co-investigator Robert H. Brown, Jr, MD, professor of neurology, University of Massachusetts Medical School, Worcester.

“The virus essentially drops off a piece of DNA, and that DNA keeps making the agent that suppresses the gene,” Dr. Brown said.

He noted that the first patient had a mutation that causes a rapidly developing, “horribly devastating” disease.

Initially, the patient’s right leg, in which movement had been worsening over several weeks, “seemed to get stronger and remain strong for quite a long time. I’ve never seen that in this kind of mutation,” said Dr. Brown.

The patient died of ALS. At autopsy, there was evidence of suppression of SOD1 in the spinal cord. There was some preservation of motor neurons on the right side of the spinal cord, which Dr. Brown called a “stunning” finding.

“We have never seen preservation of motor neurons in an autopsy of a patient with this kind of mutation before,” he said.

Prior to the patient’s death, there were some initial signs of a decrease of SOD1 in CSF. However, the patient developed an inflammatory response in the lining of the CSF known as meningoradiculitis.

“In that setting, the SOD1 level went back up, so we could not say that we produced a significant lasting decrease,” Dr. Brown said.
 

One and done

Because meningoradiculitis occurred in the first patient, immunosuppressive drugs were administered to the second patient.

The functional status and vital capacity of the second patient were relatively stable during a 60-week period, a course that could be typical of the slow disease progression in patients with this SOD1 genotype.

As with the first patient, this man did not experience a substantial change in SOD1 protein levels in CSF, and he did not show clinical improvement.

The main advantage of a viral gene therapy is that it could be a one-time treatment; ideally, it could be used to replace a single missing gene in conditions such as cystic fibrosis. “The hope is that the virus will drop off the gene modulator or the gene itself of interest, depending on the disease, and that the gene will be there more or less indefinitely,” said Dr. Brown. “So the cliché is, ‘one and done’—if all goes well.”

This small study illustrates that gene therapy safely “turns off genes and that the extent of suppression of genes can be significant,” said Dr. Brown.

Most SOD1 mutations could be treated with this microRNA viral vector, he added. More than 180 such mutations have been identified in ALS.

Additional studies are now needed to determine the results of this method in a larger number of patients who have ALS with SOD1 mutations, the investigators wrote.
 

Within reach

Both studies are encouraging in that they show that a precision-medicine approach to ALS associated with single mutated genes “may be within reach,” said Dr. Hardiman.

She noted that gene therapies have been used successfully in other motor neuron conditions. For example, an ASO and a viral vector have “very significant efficacy” in a form of spinal muscular atrophy that occurs in infants. “So the underlying proof of principle is already there.”

The reduction in SOD1 levels among the highest-dose tofersen group in the first study indicates “target engagement,” Dr. Hardiman said.

In that study, the documented decreased protein in the CSF appeared to be dose related, as was the effect for neurofilaments, which is biomarker evidence of neuronal damage, she noted.

In the second study, the pathologic evidence from the first patient also suggests “evidence of target engagement,” Dr. Hardiman said.

However, she added, “We don’t know very much about the outcome of the second case other than immunosuppression seemed to be beneficial.”
 

New hope

Both studies have caveats, said Dr. Hardiman. For example, it is unclear whether the treatments would be beneficial for every variant in SOD1.

“These are very expensive therapies, and we will need to have some level of certainty in order to be able to determine whether this should be a treatment for a patient or not,” said Dr. Hardiman.

She also noted that the studies were not powered to provide evidence of efficacy and that they raise questions about the accuracy of the ALSFRS-R.

One issue is that the respiratory part of that scale is “very insensitive”; another is that the scale doesn’t capture nonmotor elements, such as cognition and behavior, she said.

Utilizing a combination of the ALSFRS-R slope and survival would “probably be more beneficial,” Dr. Hardiman said.

Understanding how to alter the genetic influence in a disorder is important to be able to identify successful treatments, Dr. Hardiman added. For example, the discovery of the BRCA gene led oncologists to develop a precision medicine approach to the treatment of breast cancer.

In regard to ALS, by starting with subgroups that have specific genomic features, “investigators are providing new hope for patients at genetic risk for this devastating fatal disease,” said Dr. Hardiman.

The first study was funded by Biogen. The second study was funded by a fellowship grant from the Alzheimer’s Association, a Jack Satter Foundation Award, the ALS Association, the Angel Fund for ALS Research, ALS Finding a Cure, ALS-One, Project ALS, the Massachusetts General Hospital, the Max Rosenfeld and Cellucci Funds for ALS Research, and several senior members of Bain Capital. Dr. Ferguson is employed by and holds stock in Biogen. Dr. Brown receives grant support from the National Institute of Neurological Disorders and Stroke. He is also co-founder of Apic Bio. Dr. Hardiman is the editor-in-chief of the Journal of Amyotrophic Lateral Sclerosis and Frontotemporal Degenerations, has consulted for Cytokinetics, Mitsubishi, and Wave, and holds research grants from Novartis and Merck. During the past 2 years, she has also been a principal investigator on ALS clinical trials sponsored by Orion and Cytokinetics and is currently on the data and safety monitoring board of Accelsior.

This article first appeared on Medscape.com.

Two early studies are raising hopes that some genetic forms of amyotrophic lateral sclerosis (ALS) can be treated. Both studies investigated potential benefits of suppressing the toxic activity in cells of a mutant gene (SOD1) that encodes superoxide dismutase 1 (SOD1) in patients with ALS.

One study investigated the antisense oligonucleotide (ASO) tofersen (Biogen); the other study examined viral vector–mediated gene suppression.

The studies’ promising results signal “the beginning of a new precision medicine–based approach towards treating ALS,” said Orla Hardiman, BSc, MB, BCh, BAO, MD, a consultant neurologist and professor of neurology at Trinity College and Beaumont Hospital in Dublin, Ireland. Dr. Hardiman co-authored an editorial that accompanied the two studies, which were published July 9 in the New England Journal of Medicine.
 

Genetic culprits

ALS is a disorder of progressive degeneration of upper and lower motor neurons. It typically leads to death from ventilatory failure within 5 years of symptom onset.

Genetic factors are responsible for about half the risk variance of ALS. In populations of European origin, variants in SOD1 account for an estimated 13% to 20% of familial ALS, although this rate varies around the world. Although SOD1 is not the most common variant in ALS, it is the one that researchers are most familiar with and has been studied in an animal model.

In the first study, investigators evaluated the safety, pharmacokinetics, and pharmacodynamics of the ASO tofersen in adults with ALS.

An ASO is a small piece of nucleic acid that enters neurons in the spinal cord and brain, explained co-investigator Toby A. Ferguson, MD, PhD, vice president and head of the neuromuscular development unit at Biogen.

ASO binds to the SOD1 gene and knocks down the SOD1 protein, which is the “toxic engine [that] drives the disease, kills neurons, and causes patients to have loss of function and eventually to die,” said Dr. Ferguson. “The ASO turns off the motor that produces that toxic protein,” he added.

Animal studies have shown that ASOs that target SOD1 messenger RNA transcripts prolong survival, improve motor performance, and reduce SOD1 protein concentrations.

The new phase 1/2 double-blind study included 50 adults at 18 sites in the United States, Canada, and four European countries. All had muscle weakness attributed to ALS and a documented SOD1 mutation. Participants were randomly assigned to receive one of four doses of tofersen—20, 40, 60, or 100 mg—or placebo. Treatment was administered via a lumbar intrathecal bolus injection. The study included a screening period followed by a 12-week intervention period and a 12-week follow-up.
 

Adverse events

A primary outcome was the incidence of adverse events (AEs) and serious AEs. Results showed that all participants reported one or more AEs. The most common AEs were headache, pain at the injection site, post–lumbar puncture syndrome, and falls. Three deaths occurred, one in the placebo group, one in the 20-mg dose group, and one in the 60-mg dose group. There were no serious AEs in the 100-mg group.

Although the investigators found an increase in cerebrospinal fluid (CSF) protein and white cell counts, there was no clear association between these observations and higher doses of tofersen or longer duration of exposure.

“We don’t know the implications of this, and it’s something we need to keep an eye on as we move these studies forward,” Dr. Ferguson said.

None of the AEs or CSF abnormalities led to trial discontinuation.

A secondary outcome was change in SOD1 protein concentration in CSF at day 85. The study showed that SOD1 concentrations decreased by 36% among the participants who received tofersen 100 mg and by lesser amounts in the patients who received lower doses. Concentrations in the placebo group were reduced by 3%.

The 36% reduction in the highest dose group is likely meaningful and “foundational to the concept of what this molecule can do,” Dr. Ferguson said.

“If the number one cause of SOD1 ALS is accumulation of toxic SOD1 protein, then the demonstration that we can reduce SOD1 protein in the CSF ... is saying that’s the first step on the way to showing the molecule is doing what it should do,” he added.
 

Emerging tool

In patients with ALS, neurofilament concentrations typically increase as the disease progresses. However, this study documented a reduction in these CSF concentrations. “One interpretation of that could be that there is less neurodegeneration or neuro injury” in patients treated with tofersen, Dr. Ferguson said.

He noted that neurofilament is “an emerging tool” for understanding neurodegeneration. It could also “be another sort of biochemical signal that the molecule is doing something important,” he added.

However, he noted that neurofilament concentration is still an exploratory marker.

Exploratory analyses suggested a possible slowing of functional loss, as measured by the ALS Functional Rating Scale–Revised (ALSFRS-R) score and the handheld dynamometry megascore. The latter assesses strength in 16 muscle groups in the arms and legs. The investigators noted that no conclusions can be drawn from these outcomes.

A post hoc analysis showed that among patients with SOD1 mutations associated with a fast-progressing disease course, the slope of clinical decline might have been gentler, and there was a greater decrease in CSF neurofilament concentration compared among those whose disease followed a slower course.

This suggests that “if you pick the right target,” even patients with severe disease can be treated, Dr. Ferguson said.

He acknowledged that in a relatively short study such as this one, it may be easier to see benefits in patients whose disease is progressing rapidly. However, he’s convinced that the treatment “would work for all SOD1 ALS patients, not just fast patients.”

Dr. Ferguson said the study investigators are encouraged by the new data, which “really suggest that we may be developing a meaningful treatment for SOD1 ALS.” However, “it’s still early” in terms of rolling out this therapy for patients with ALS, he said.

The safety and efficacy of tofersen are currently being evaluated in a phase 3, randomized, double-blind, placebo-controlled trial.

Limitations of the current study were the small number of participants, the short duration of treatment and follow-up, the exploratory nature of efficacy outcomes, and the post hoc methods for defining the fast-progressing subgroup.

Although an advantage of tofersen is that it can enter the nucleus of the cell, perhaps boosting effectiveness, a drawback might be that patients need several treatments administered via lumbar puncture. Following three initial doses, the drug is given every month.

An alternative approach might be a viral vector approach.
 

“Stunning” finding

In the second study, investigators assessed the safety of a single intrathecal infusion of a viral vector therapy designed to target SOD1 in two patients with familial ALS. The two patients were a 22-year-old man whose mother had died of ALS at age 45 and a 56-year-old man who had a family history of ALS.

The aim of the viral vector therapy is to continually suppress mutant gene activity, said study co-investigator Robert H. Brown, Jr, MD, professor of neurology, University of Massachusetts Medical School, Worcester.

“The virus essentially drops off a piece of DNA, and that DNA keeps making the agent that suppresses the gene,” Dr. Brown said.

He noted that the first patient had a mutation that causes a rapidly developing, “horribly devastating” disease.

Initially, the patient’s right leg, in which movement had been worsening over several weeks, “seemed to get stronger and remain strong for quite a long time. I’ve never seen that in this kind of mutation,” said Dr. Brown.

The patient died of ALS. At autopsy, there was evidence of suppression of SOD1 in the spinal cord. There was some preservation of motor neurons on the right side of the spinal cord, which Dr. Brown called a “stunning” finding.

“We have never seen preservation of motor neurons in an autopsy of a patient with this kind of mutation before,” he said.

Prior to the patient’s death, there were some initial signs of a decrease of SOD1 in CSF. However, the patient developed an inflammatory response in the lining of the CSF known as meningoradiculitis.

“In that setting, the SOD1 level went back up, so we could not say that we produced a significant lasting decrease,” Dr. Brown said.
 

One and done

Because meningoradiculitis occurred in the first patient, immunosuppressive drugs were administered to the second patient.

The functional status and vital capacity of the second patient were relatively stable during a 60-week period, a course that could be typical of the slow disease progression in patients with this SOD1 genotype.

As with the first patient, this man did not experience a substantial change in SOD1 protein levels in CSF, and he did not show clinical improvement.

The main advantage of a viral gene therapy is that it could be a one-time treatment; ideally, it could be used to replace a single missing gene in conditions such as cystic fibrosis. “The hope is that the virus will drop off the gene modulator or the gene itself of interest, depending on the disease, and that the gene will be there more or less indefinitely,” said Dr. Brown. “So the cliché is, ‘one and done’—if all goes well.”

This small study illustrates that gene therapy safely “turns off genes and that the extent of suppression of genes can be significant,” said Dr. Brown.

Most SOD1 mutations could be treated with this microRNA viral vector, he added. More than 180 such mutations have been identified in ALS.

Additional studies are now needed to determine the results of this method in a larger number of patients who have ALS with SOD1 mutations, the investigators wrote.
 

Within reach

Both studies are encouraging in that they show that a precision-medicine approach to ALS associated with single mutated genes “may be within reach,” said Dr. Hardiman.

She noted that gene therapies have been used successfully in other motor neuron conditions. For example, an ASO and a viral vector have “very significant efficacy” in a form of spinal muscular atrophy that occurs in infants. “So the underlying proof of principle is already there.”

The reduction in SOD1 levels among the highest-dose tofersen group in the first study indicates “target engagement,” Dr. Hardiman said.

In that study, the documented decreased protein in the CSF appeared to be dose related, as was the effect for neurofilaments, which is biomarker evidence of neuronal damage, she noted.

In the second study, the pathologic evidence from the first patient also suggests “evidence of target engagement,” Dr. Hardiman said.

However, she added, “We don’t know very much about the outcome of the second case other than immunosuppression seemed to be beneficial.”
 

New hope

Both studies have caveats, said Dr. Hardiman. For example, it is unclear whether the treatments would be beneficial for every variant in SOD1.

“These are very expensive therapies, and we will need to have some level of certainty in order to be able to determine whether this should be a treatment for a patient or not,” said Dr. Hardiman.

She also noted that the studies were not powered to provide evidence of efficacy and that they raise questions about the accuracy of the ALSFRS-R.

One issue is that the respiratory part of that scale is “very insensitive”; another is that the scale doesn’t capture nonmotor elements, such as cognition and behavior, she said.

Utilizing a combination of the ALSFRS-R slope and survival would “probably be more beneficial,” Dr. Hardiman said.

Understanding how to alter the genetic influence in a disorder is important to be able to identify successful treatments, Dr. Hardiman added. For example, the discovery of the BRCA gene led oncologists to develop a precision medicine approach to the treatment of breast cancer.

In regard to ALS, by starting with subgroups that have specific genomic features, “investigators are providing new hope for patients at genetic risk for this devastating fatal disease,” said Dr. Hardiman.

The first study was funded by Biogen. The second study was funded by a fellowship grant from the Alzheimer’s Association, a Jack Satter Foundation Award, the ALS Association, the Angel Fund for ALS Research, ALS Finding a Cure, ALS-One, Project ALS, the Massachusetts General Hospital, the Max Rosenfeld and Cellucci Funds for ALS Research, and several senior members of Bain Capital. Dr. Ferguson is employed by and holds stock in Biogen. Dr. Brown receives grant support from the National Institute of Neurological Disorders and Stroke. He is also co-founder of Apic Bio. Dr. Hardiman is the editor-in-chief of the Journal of Amyotrophic Lateral Sclerosis and Frontotemporal Degenerations, has consulted for Cytokinetics, Mitsubishi, and Wave, and holds research grants from Novartis and Merck. During the past 2 years, she has also been a principal investigator on ALS clinical trials sponsored by Orion and Cytokinetics and is currently on the data and safety monitoring board of Accelsior.

This article first appeared on Medscape.com.

Two early studies are raising hopes that some genetic forms of amyotrophic lateral sclerosis (ALS) can be treated. Both studies investigated potential benefits of suppressing the toxic activity in cells of a mutant gene (SOD1) that encodes superoxide dismutase 1 (SOD1) in patients with ALS.

One study investigated the antisense oligonucleotide (ASO) tofersen (Biogen); the other study examined viral vector–mediated gene suppression.

The studies’ promising results signal “the beginning of a new precision medicine–based approach towards treating ALS,” said Orla Hardiman, BSc, MB, BCh, BAO, MD, a consultant neurologist and professor of neurology at Trinity College and Beaumont Hospital in Dublin, Ireland. Dr. Hardiman co-authored an editorial that accompanied the two studies, which were published July 9 in the New England Journal of Medicine.
 

Genetic culprits

ALS is a disorder of progressive degeneration of upper and lower motor neurons. It typically leads to death from ventilatory failure within 5 years of symptom onset.

Genetic factors are responsible for about half the risk variance of ALS. In populations of European origin, variants in SOD1 account for an estimated 13% to 20% of familial ALS, although this rate varies around the world. Although SOD1 is not the most common variant in ALS, it is the one that researchers are most familiar with and has been studied in an animal model.

In the first study, investigators evaluated the safety, pharmacokinetics, and pharmacodynamics of the ASO tofersen in adults with ALS.

An ASO is a small piece of nucleic acid that enters neurons in the spinal cord and brain, explained co-investigator Toby A. Ferguson, MD, PhD, vice president and head of the neuromuscular development unit at Biogen.

ASO binds to the SOD1 gene and knocks down the SOD1 protein, which is the “toxic engine [that] drives the disease, kills neurons, and causes patients to have loss of function and eventually to die,” said Dr. Ferguson. “The ASO turns off the motor that produces that toxic protein,” he added.

Animal studies have shown that ASOs that target SOD1 messenger RNA transcripts prolong survival, improve motor performance, and reduce SOD1 protein concentrations.

The new phase 1/2 double-blind study included 50 adults at 18 sites in the United States, Canada, and four European countries. All had muscle weakness attributed to ALS and a documented SOD1 mutation. Participants were randomly assigned to receive one of four doses of tofersen—20, 40, 60, or 100 mg—or placebo. Treatment was administered via a lumbar intrathecal bolus injection. The study included a screening period followed by a 12-week intervention period and a 12-week follow-up.
 

Adverse events

A primary outcome was the incidence of adverse events (AEs) and serious AEs. Results showed that all participants reported one or more AEs. The most common AEs were headache, pain at the injection site, post–lumbar puncture syndrome, and falls. Three deaths occurred, one in the placebo group, one in the 20-mg dose group, and one in the 60-mg dose group. There were no serious AEs in the 100-mg group.

Although the investigators found an increase in cerebrospinal fluid (CSF) protein and white cell counts, there was no clear association between these observations and higher doses of tofersen or longer duration of exposure.

“We don’t know the implications of this, and it’s something we need to keep an eye on as we move these studies forward,” Dr. Ferguson said.

None of the AEs or CSF abnormalities led to trial discontinuation.

A secondary outcome was change in SOD1 protein concentration in CSF at day 85. The study showed that SOD1 concentrations decreased by 36% among the participants who received tofersen 100 mg and by lesser amounts in the patients who received lower doses. Concentrations in the placebo group were reduced by 3%.

The 36% reduction in the highest dose group is likely meaningful and “foundational to the concept of what this molecule can do,” Dr. Ferguson said.

“If the number one cause of SOD1 ALS is accumulation of toxic SOD1 protein, then the demonstration that we can reduce SOD1 protein in the CSF ... is saying that’s the first step on the way to showing the molecule is doing what it should do,” he added.
 

Emerging tool

In patients with ALS, neurofilament concentrations typically increase as the disease progresses. However, this study documented a reduction in these CSF concentrations. “One interpretation of that could be that there is less neurodegeneration or neuro injury” in patients treated with tofersen, Dr. Ferguson said.

He noted that neurofilament is “an emerging tool” for understanding neurodegeneration. It could also “be another sort of biochemical signal that the molecule is doing something important,” he added.

However, he noted that neurofilament concentration is still an exploratory marker.

Exploratory analyses suggested a possible slowing of functional loss, as measured by the ALS Functional Rating Scale–Revised (ALSFRS-R) score and the handheld dynamometry megascore. The latter assesses strength in 16 muscle groups in the arms and legs. The investigators noted that no conclusions can be drawn from these outcomes.

A post hoc analysis showed that among patients with SOD1 mutations associated with a fast-progressing disease course, the slope of clinical decline might have been gentler, and there was a greater decrease in CSF neurofilament concentration compared among those whose disease followed a slower course.

This suggests that “if you pick the right target,” even patients with severe disease can be treated, Dr. Ferguson said.

He acknowledged that in a relatively short study such as this one, it may be easier to see benefits in patients whose disease is progressing rapidly. However, he’s convinced that the treatment “would work for all SOD1 ALS patients, not just fast patients.”

Dr. Ferguson said the study investigators are encouraged by the new data, which “really suggest that we may be developing a meaningful treatment for SOD1 ALS.” However, “it’s still early” in terms of rolling out this therapy for patients with ALS, he said.

The safety and efficacy of tofersen are currently being evaluated in a phase 3, randomized, double-blind, placebo-controlled trial.

Limitations of the current study were the small number of participants, the short duration of treatment and follow-up, the exploratory nature of efficacy outcomes, and the post hoc methods for defining the fast-progressing subgroup.

Although an advantage of tofersen is that it can enter the nucleus of the cell, perhaps boosting effectiveness, a drawback might be that patients need several treatments administered via lumbar puncture. Following three initial doses, the drug is given every month.

An alternative approach might be a viral vector approach.
 

“Stunning” finding

In the second study, investigators assessed the safety of a single intrathecal infusion of a viral vector therapy designed to target SOD1 in two patients with familial ALS. The two patients were a 22-year-old man whose mother had died of ALS at age 45 and a 56-year-old man who had a family history of ALS.

The aim of the viral vector therapy is to continually suppress mutant gene activity, said study co-investigator Robert H. Brown, Jr, MD, professor of neurology, University of Massachusetts Medical School, Worcester.

“The virus essentially drops off a piece of DNA, and that DNA keeps making the agent that suppresses the gene,” Dr. Brown said.

He noted that the first patient had a mutation that causes a rapidly developing, “horribly devastating” disease.

Initially, the patient’s right leg, in which movement had been worsening over several weeks, “seemed to get stronger and remain strong for quite a long time. I’ve never seen that in this kind of mutation,” said Dr. Brown.

The patient died of ALS. At autopsy, there was evidence of suppression of SOD1 in the spinal cord. There was some preservation of motor neurons on the right side of the spinal cord, which Dr. Brown called a “stunning” finding.

“We have never seen preservation of motor neurons in an autopsy of a patient with this kind of mutation before,” he said.

Prior to the patient’s death, there were some initial signs of a decrease of SOD1 in CSF. However, the patient developed an inflammatory response in the lining of the CSF known as meningoradiculitis.

“In that setting, the SOD1 level went back up, so we could not say that we produced a significant lasting decrease,” Dr. Brown said.
 

One and done

Because meningoradiculitis occurred in the first patient, immunosuppressive drugs were administered to the second patient.

The functional status and vital capacity of the second patient were relatively stable during a 60-week period, a course that could be typical of the slow disease progression in patients with this SOD1 genotype.

As with the first patient, this man did not experience a substantial change in SOD1 protein levels in CSF, and he did not show clinical improvement.

The main advantage of a viral gene therapy is that it could be a one-time treatment; ideally, it could be used to replace a single missing gene in conditions such as cystic fibrosis. “The hope is that the virus will drop off the gene modulator or the gene itself of interest, depending on the disease, and that the gene will be there more or less indefinitely,” said Dr. Brown. “So the cliché is, ‘one and done’—if all goes well.”

This small study illustrates that gene therapy safely “turns off genes and that the extent of suppression of genes can be significant,” said Dr. Brown.

Most SOD1 mutations could be treated with this microRNA viral vector, he added. More than 180 such mutations have been identified in ALS.

Additional studies are now needed to determine the results of this method in a larger number of patients who have ALS with SOD1 mutations, the investigators wrote.
 

Within reach

Both studies are encouraging in that they show that a precision-medicine approach to ALS associated with single mutated genes “may be within reach,” said Dr. Hardiman.

She noted that gene therapies have been used successfully in other motor neuron conditions. For example, an ASO and a viral vector have “very significant efficacy” in a form of spinal muscular atrophy that occurs in infants. “So the underlying proof of principle is already there.”

The reduction in SOD1 levels among the highest-dose tofersen group in the first study indicates “target engagement,” Dr. Hardiman said.

In that study, the documented decreased protein in the CSF appeared to be dose related, as was the effect for neurofilaments, which is biomarker evidence of neuronal damage, she noted.

In the second study, the pathologic evidence from the first patient also suggests “evidence of target engagement,” Dr. Hardiman said.

However, she added, “We don’t know very much about the outcome of the second case other than immunosuppression seemed to be beneficial.”
 

New hope

Both studies have caveats, said Dr. Hardiman. For example, it is unclear whether the treatments would be beneficial for every variant in SOD1.

“These are very expensive therapies, and we will need to have some level of certainty in order to be able to determine whether this should be a treatment for a patient or not,” said Dr. Hardiman.

She also noted that the studies were not powered to provide evidence of efficacy and that they raise questions about the accuracy of the ALSFRS-R.

One issue is that the respiratory part of that scale is “very insensitive”; another is that the scale doesn’t capture nonmotor elements, such as cognition and behavior, she said.

Utilizing a combination of the ALSFRS-R slope and survival would “probably be more beneficial,” Dr. Hardiman said.

Understanding how to alter the genetic influence in a disorder is important to be able to identify successful treatments, Dr. Hardiman added. For example, the discovery of the BRCA gene led oncologists to develop a precision medicine approach to the treatment of breast cancer.

In regard to ALS, by starting with subgroups that have specific genomic features, “investigators are providing new hope for patients at genetic risk for this devastating fatal disease,” said Dr. Hardiman.

The first study was funded by Biogen. The second study was funded by a fellowship grant from the Alzheimer’s Association, a Jack Satter Foundation Award, the ALS Association, the Angel Fund for ALS Research, ALS Finding a Cure, ALS-One, Project ALS, the Massachusetts General Hospital, the Max Rosenfeld and Cellucci Funds for ALS Research, and several senior members of Bain Capital. Dr. Ferguson is employed by and holds stock in Biogen. Dr. Brown receives grant support from the National Institute of Neurological Disorders and Stroke. He is also co-founder of Apic Bio. Dr. Hardiman is the editor-in-chief of the Journal of Amyotrophic Lateral Sclerosis and Frontotemporal Degenerations, has consulted for Cytokinetics, Mitsubishi, and Wave, and holds research grants from Novartis and Merck. During the past 2 years, she has also been a principal investigator on ALS clinical trials sponsored by Orion and Cytokinetics and is currently on the data and safety monitoring board of Accelsior.

This article first appeared on Medscape.com.