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When the only clinical choices are ‘lose-lose’
Among the many tolls inflicted on health care workers by COVID-19 is one that is not as easily measured as rates of death or disease, but is no less tangible: moral injury. This is the term by which we describe the psychological, social, and spiritual impact of high-stakes situations that lead to the betrayal or transgression of our own deeply held moral beliefs and values.
The current pandemic has provided innumerable such situations that can increase the risk for moral injury, whether we deal directly with patients infected by the coronavirus or not. Telling family members they cannot visit critically ill loved ones. Delaying code activities, even momentarily, to get fully protected with personal protective equipment. Seeing patients who have delayed their necessary or preventive care. Using video rather than touch to reassure people.
Knowing that we are following guidelines from the Centers for Disease Control and Prevention does not stop our feelings of guilt. The longer this pandemic goes on, the more likely it is that these situations will begin to take a toll on us.
For most of us, being exposed to moral injuries is new; they have historically been most associated with severe traumatic wartime experiences. Soldiers, philosophers, and writers have described the ethical dilemmas inherent in war for as long as recorded history. But the use of this term is a more recent development, which the Moral Injury Project at Syracuse (N.Y.) University describes as probably originating in the Vietnam War–era writings of veteran and peace activist Camillo “Mac” Bica and psychiatrist Jonathan Shay. Examples of wartime events that have been thought to lead to moral injury include: causing the harm or death of civilians, knowingly but without alternatives, or accidentally; failing to provide medical aid to an injured civilian or service member; and following orders that were illegal, immoral, and/or against the rules of engagement or the Geneva Conventions.
However, the occurrence of moral injuries in modern health care is increasingly being reported, primarily as an adverse effect of health care inefficiencies that can contribute to burnout. COVID-19 has now provided an array of additional stressors that can cause moral injuries among health care workers. A recent guidance document on moral injury published by the American Psychiatric Association noted that, in the context of a public health disaster, such as COVID-19, it is sometimes necessary to transition from ordinary standards of care to those more appropriate in a crisis, as in wartime. This forces us all to confront challenging questions for which there may be no clear answers, and to make “lose-lose” choices in which no one involved – patients, family, or clinicians – ends up feeling satisfied or even comfortable.
Our lives have been altered significantly, and for many, completely turned upside down by enormous sacrifices and tragic losses. Globally, physicians account for over half of healthcare worker deaths. In the United States alone, over 900 health care workers have died of COVID-19.
Most of us have felt the symptoms of moral injury: frustration, anger, disgust, guilt. A recent report describes three levels of stressors in health care occurring during the pandemic, which are not dissimilar to those wartime events described previously.
- Severe moral stressors, such as the denial of treatment to a COVID-19 patient owing to lack of resources, the inability to provide optimal care to non–COVID-19 patients for many reasons, and concern about passing COVID to loved ones.
- Moderate moral stressors, such as preventing visitors, especially to dying patients, triaging patients for healthcare services with inadequate information, and trying to solve the tension between the need for self-preservation and the need to treat.
- Lower-level but common moral challenges, especially in the community – for example, seeing others not protecting the community by hoarding food, gathering for large parties, and not social distancing or wearing masks. Such stressors lead to frustration and contempt, especially from healthcare workers making personal sacrifices and who may be at risk for infection caused by these behaviors.
Every one of us is affected by these stressors. I certainly am.
What are the outcomes? We know that moral injuries are a risk factor for the development of mental health problems and burnout, and not surprisingly we are seeing that mental health problems, suicidality, and substance use disorders have increased markedly during COVID-19, as recently detailed by the CDC.
Common emotions that occur in response to moral injuries are: feelings of guilt, shame, anger, sadness, anxiety, and disgust; intrapersonal outcomes, including lowered self-esteem, high self-criticism, and beliefs about being bad, damaged, unworthy, failing, or weak; interpersonal outcomes, including loss of faith in people, avoidance of intimacy, and lack of trust in authority figures; and existential and spiritual outcomes, including loss of faith in previous religious beliefs and no longer believing in a just world.
Moral injuries tend to originate primarily from systems-based problems, as we have seen with the lack of concerted national approaches to the pandemic. On the positive side, solutions typically also involve systems-based changes, which in this case may mean changes in leadership styles nationally and locally, as well as changes in the culture of medicine and the way healthcare is practiced and managed in the modern era. We are starting to see some of those changes with the increased use of telemedicine and health technologies, as well as more of a focus on the well-being of health care workers, now deemed “essential.”
As individuals, we are not helpless. There are things we can do in our workplaces to create change. I suggest:
- Acknowledge that you, like me, are affected by these stressors. This is not a secret, and you should not be ashamed of your feelings.
- Talk with your colleagues, loved ones, and friends about how you and they are affected. You are not alone. Encourage others to share their thoughts, stories, and feelings.
- Put this topic on your meeting and departmental agendas and discuss these moral issues openly with your colleagues. Allow sufficient time to engage in open dialogue.
- Work out ways of assisting those who are in high-risk situations, especially for moderate to severe injuries. Be supportive toward those affected.
- Modify policies and change rosters and rotate staff between high- and low-stress roles. Protect and support at-risk colleagues.
- Think about difficult ethical decisions in advance so they can be made by groups, not individuals, and certainly not “on the fly.”
- Keep everyone in your workplace constantly informed, especially of impending staff or equipment shortages.
- Maintain your inherent self-care and resilience with rest, good nutrition, sleep, exercise, love, caring, socialization, and work-life balance.
- Be prepared to access the many professional support services available in our community if you are intensely distressed or if the above suggestions are not enough.
Remember, we are in this together and will find strength in each other. This too will pass.
This article first appeared on Medscape.com.
Among the many tolls inflicted on health care workers by COVID-19 is one that is not as easily measured as rates of death or disease, but is no less tangible: moral injury. This is the term by which we describe the psychological, social, and spiritual impact of high-stakes situations that lead to the betrayal or transgression of our own deeply held moral beliefs and values.
The current pandemic has provided innumerable such situations that can increase the risk for moral injury, whether we deal directly with patients infected by the coronavirus or not. Telling family members they cannot visit critically ill loved ones. Delaying code activities, even momentarily, to get fully protected with personal protective equipment. Seeing patients who have delayed their necessary or preventive care. Using video rather than touch to reassure people.
Knowing that we are following guidelines from the Centers for Disease Control and Prevention does not stop our feelings of guilt. The longer this pandemic goes on, the more likely it is that these situations will begin to take a toll on us.
For most of us, being exposed to moral injuries is new; they have historically been most associated with severe traumatic wartime experiences. Soldiers, philosophers, and writers have described the ethical dilemmas inherent in war for as long as recorded history. But the use of this term is a more recent development, which the Moral Injury Project at Syracuse (N.Y.) University describes as probably originating in the Vietnam War–era writings of veteran and peace activist Camillo “Mac” Bica and psychiatrist Jonathan Shay. Examples of wartime events that have been thought to lead to moral injury include: causing the harm or death of civilians, knowingly but without alternatives, or accidentally; failing to provide medical aid to an injured civilian or service member; and following orders that were illegal, immoral, and/or against the rules of engagement or the Geneva Conventions.
However, the occurrence of moral injuries in modern health care is increasingly being reported, primarily as an adverse effect of health care inefficiencies that can contribute to burnout. COVID-19 has now provided an array of additional stressors that can cause moral injuries among health care workers. A recent guidance document on moral injury published by the American Psychiatric Association noted that, in the context of a public health disaster, such as COVID-19, it is sometimes necessary to transition from ordinary standards of care to those more appropriate in a crisis, as in wartime. This forces us all to confront challenging questions for which there may be no clear answers, and to make “lose-lose” choices in which no one involved – patients, family, or clinicians – ends up feeling satisfied or even comfortable.
Our lives have been altered significantly, and for many, completely turned upside down by enormous sacrifices and tragic losses. Globally, physicians account for over half of healthcare worker deaths. In the United States alone, over 900 health care workers have died of COVID-19.
Most of us have felt the symptoms of moral injury: frustration, anger, disgust, guilt. A recent report describes three levels of stressors in health care occurring during the pandemic, which are not dissimilar to those wartime events described previously.
- Severe moral stressors, such as the denial of treatment to a COVID-19 patient owing to lack of resources, the inability to provide optimal care to non–COVID-19 patients for many reasons, and concern about passing COVID to loved ones.
- Moderate moral stressors, such as preventing visitors, especially to dying patients, triaging patients for healthcare services with inadequate information, and trying to solve the tension between the need for self-preservation and the need to treat.
- Lower-level but common moral challenges, especially in the community – for example, seeing others not protecting the community by hoarding food, gathering for large parties, and not social distancing or wearing masks. Such stressors lead to frustration and contempt, especially from healthcare workers making personal sacrifices and who may be at risk for infection caused by these behaviors.
Every one of us is affected by these stressors. I certainly am.
What are the outcomes? We know that moral injuries are a risk factor for the development of mental health problems and burnout, and not surprisingly we are seeing that mental health problems, suicidality, and substance use disorders have increased markedly during COVID-19, as recently detailed by the CDC.
Common emotions that occur in response to moral injuries are: feelings of guilt, shame, anger, sadness, anxiety, and disgust; intrapersonal outcomes, including lowered self-esteem, high self-criticism, and beliefs about being bad, damaged, unworthy, failing, or weak; interpersonal outcomes, including loss of faith in people, avoidance of intimacy, and lack of trust in authority figures; and existential and spiritual outcomes, including loss of faith in previous religious beliefs and no longer believing in a just world.
Moral injuries tend to originate primarily from systems-based problems, as we have seen with the lack of concerted national approaches to the pandemic. On the positive side, solutions typically also involve systems-based changes, which in this case may mean changes in leadership styles nationally and locally, as well as changes in the culture of medicine and the way healthcare is practiced and managed in the modern era. We are starting to see some of those changes with the increased use of telemedicine and health technologies, as well as more of a focus on the well-being of health care workers, now deemed “essential.”
As individuals, we are not helpless. There are things we can do in our workplaces to create change. I suggest:
- Acknowledge that you, like me, are affected by these stressors. This is not a secret, and you should not be ashamed of your feelings.
- Talk with your colleagues, loved ones, and friends about how you and they are affected. You are not alone. Encourage others to share their thoughts, stories, and feelings.
- Put this topic on your meeting and departmental agendas and discuss these moral issues openly with your colleagues. Allow sufficient time to engage in open dialogue.
- Work out ways of assisting those who are in high-risk situations, especially for moderate to severe injuries. Be supportive toward those affected.
- Modify policies and change rosters and rotate staff between high- and low-stress roles. Protect and support at-risk colleagues.
- Think about difficult ethical decisions in advance so they can be made by groups, not individuals, and certainly not “on the fly.”
- Keep everyone in your workplace constantly informed, especially of impending staff or equipment shortages.
- Maintain your inherent self-care and resilience with rest, good nutrition, sleep, exercise, love, caring, socialization, and work-life balance.
- Be prepared to access the many professional support services available in our community if you are intensely distressed or if the above suggestions are not enough.
Remember, we are in this together and will find strength in each other. This too will pass.
This article first appeared on Medscape.com.
Among the many tolls inflicted on health care workers by COVID-19 is one that is not as easily measured as rates of death or disease, but is no less tangible: moral injury. This is the term by which we describe the psychological, social, and spiritual impact of high-stakes situations that lead to the betrayal or transgression of our own deeply held moral beliefs and values.
The current pandemic has provided innumerable such situations that can increase the risk for moral injury, whether we deal directly with patients infected by the coronavirus or not. Telling family members they cannot visit critically ill loved ones. Delaying code activities, even momentarily, to get fully protected with personal protective equipment. Seeing patients who have delayed their necessary or preventive care. Using video rather than touch to reassure people.
Knowing that we are following guidelines from the Centers for Disease Control and Prevention does not stop our feelings of guilt. The longer this pandemic goes on, the more likely it is that these situations will begin to take a toll on us.
For most of us, being exposed to moral injuries is new; they have historically been most associated with severe traumatic wartime experiences. Soldiers, philosophers, and writers have described the ethical dilemmas inherent in war for as long as recorded history. But the use of this term is a more recent development, which the Moral Injury Project at Syracuse (N.Y.) University describes as probably originating in the Vietnam War–era writings of veteran and peace activist Camillo “Mac” Bica and psychiatrist Jonathan Shay. Examples of wartime events that have been thought to lead to moral injury include: causing the harm or death of civilians, knowingly but without alternatives, or accidentally; failing to provide medical aid to an injured civilian or service member; and following orders that were illegal, immoral, and/or against the rules of engagement or the Geneva Conventions.
However, the occurrence of moral injuries in modern health care is increasingly being reported, primarily as an adverse effect of health care inefficiencies that can contribute to burnout. COVID-19 has now provided an array of additional stressors that can cause moral injuries among health care workers. A recent guidance document on moral injury published by the American Psychiatric Association noted that, in the context of a public health disaster, such as COVID-19, it is sometimes necessary to transition from ordinary standards of care to those more appropriate in a crisis, as in wartime. This forces us all to confront challenging questions for which there may be no clear answers, and to make “lose-lose” choices in which no one involved – patients, family, or clinicians – ends up feeling satisfied or even comfortable.
Our lives have been altered significantly, and for many, completely turned upside down by enormous sacrifices and tragic losses. Globally, physicians account for over half of healthcare worker deaths. In the United States alone, over 900 health care workers have died of COVID-19.
Most of us have felt the symptoms of moral injury: frustration, anger, disgust, guilt. A recent report describes three levels of stressors in health care occurring during the pandemic, which are not dissimilar to those wartime events described previously.
- Severe moral stressors, such as the denial of treatment to a COVID-19 patient owing to lack of resources, the inability to provide optimal care to non–COVID-19 patients for many reasons, and concern about passing COVID to loved ones.
- Moderate moral stressors, such as preventing visitors, especially to dying patients, triaging patients for healthcare services with inadequate information, and trying to solve the tension between the need for self-preservation and the need to treat.
- Lower-level but common moral challenges, especially in the community – for example, seeing others not protecting the community by hoarding food, gathering for large parties, and not social distancing or wearing masks. Such stressors lead to frustration and contempt, especially from healthcare workers making personal sacrifices and who may be at risk for infection caused by these behaviors.
Every one of us is affected by these stressors. I certainly am.
What are the outcomes? We know that moral injuries are a risk factor for the development of mental health problems and burnout, and not surprisingly we are seeing that mental health problems, suicidality, and substance use disorders have increased markedly during COVID-19, as recently detailed by the CDC.
Common emotions that occur in response to moral injuries are: feelings of guilt, shame, anger, sadness, anxiety, and disgust; intrapersonal outcomes, including lowered self-esteem, high self-criticism, and beliefs about being bad, damaged, unworthy, failing, or weak; interpersonal outcomes, including loss of faith in people, avoidance of intimacy, and lack of trust in authority figures; and existential and spiritual outcomes, including loss of faith in previous religious beliefs and no longer believing in a just world.
Moral injuries tend to originate primarily from systems-based problems, as we have seen with the lack of concerted national approaches to the pandemic. On the positive side, solutions typically also involve systems-based changes, which in this case may mean changes in leadership styles nationally and locally, as well as changes in the culture of medicine and the way healthcare is practiced and managed in the modern era. We are starting to see some of those changes with the increased use of telemedicine and health technologies, as well as more of a focus on the well-being of health care workers, now deemed “essential.”
As individuals, we are not helpless. There are things we can do in our workplaces to create change. I suggest:
- Acknowledge that you, like me, are affected by these stressors. This is not a secret, and you should not be ashamed of your feelings.
- Talk with your colleagues, loved ones, and friends about how you and they are affected. You are not alone. Encourage others to share their thoughts, stories, and feelings.
- Put this topic on your meeting and departmental agendas and discuss these moral issues openly with your colleagues. Allow sufficient time to engage in open dialogue.
- Work out ways of assisting those who are in high-risk situations, especially for moderate to severe injuries. Be supportive toward those affected.
- Modify policies and change rosters and rotate staff between high- and low-stress roles. Protect and support at-risk colleagues.
- Think about difficult ethical decisions in advance so they can be made by groups, not individuals, and certainly not “on the fly.”
- Keep everyone in your workplace constantly informed, especially of impending staff or equipment shortages.
- Maintain your inherent self-care and resilience with rest, good nutrition, sleep, exercise, love, caring, socialization, and work-life balance.
- Be prepared to access the many professional support services available in our community if you are intensely distressed or if the above suggestions are not enough.
Remember, we are in this together and will find strength in each other. This too will pass.
This article first appeared on Medscape.com.
Scrubs ad that insulted women and DOs pulled after outcry
A video that advertised scrubs but denigrated women and DOs has been removed from the company’s website after fierce backlash.
On Tuesday Kevin Klauer, DO, EJD, directed this tweet to the medical uniform company Figs: “@wearfigs REMOVE YOUR DO offensive web ad immediately or the @AOAforDOs will proceed promptly with a defamation lawsuit on behalf of our members and profession.”
Also on Tuesday, the American Association of Colleges of Osteopathic Medicine demanded a public apology.
The video ad featured a woman carrying a “Medical Terminology for Dummies” book upside down while modeling the pink scrubs from all angles and dancing. At one point in the ad, the camera zooms in on the badge clipped to her waistband that read “DO.”
Agnieszka Solberg, MD, a vascular and interventional radiologist and assistant clinical professor at the University of North Dakota in Grand Forks, was among those voicing pointed criticism on social media.
“This was another hit for our DO colleagues,” she said in an interview, emphasizing that MDs and DOs provide the same level of care.
AACOM tweeted: “We are outraged women physicians & doctors of osteopathic medicine are still attacked in ignorant marketing campaigns. A company like @wearfigs should be ashamed for promoting these stereotypes. We demand the respect we’ve earned AND a public apology.”
Dr. Solberg says this is not the first offense by the company. She said she had stopped buying the company’s scrubs a year ago because the ads “have been portraying female providers as dumb and silly. This was the final straw.”
She said the timing of the ad is suspect as DOs had been swept into a storm of negativity earlier this month, as Medscape Medical News reported, when some questioned the qualifications of President Donald Trump’s physician, Sean Conley, who is a DO.
The scrubs ad ignited criticism across specialties, provider levels, and genders.
Jessica K. Willett, MD, tweeted: “As women physicians in 2020, we still struggle to be taken seriously compared to our male counterparts, as we battle stereotypes like THIS EXACT ONE. We expect the brands we support to reflect the badasses we are.”
The company responded to her tweet: “Thank you so much for the feedback! Totally not our intent – we’re taking down both the men’s and women’s versions of this ASAP! I really appreciate you taking the time to share this.”
The company did not respond to a request for comment but issued an apology on social media: “A lot of you guys have pointed out an insensitive video we had on our site – we are incredibly sorry for any hurt this has caused you, especially our female DOs (who are amazing!) FIGS is a female founded company whose only mission is to make you guys feel awesome.”
The Los Angeles–based company, which Forbes estimated will make $250 million in sales this year, was founded by co-CEOs Heather Hasson and Trina Spear.
A med student wrote on Twitter: “As a female and a DO student, how would I ever “feel awesome” about myself knowing that this is how you view me??? And how you want others to view me??? Women and DO’s have fought stereotypes way too long for you to go ahead and put this out there. Do better.”
Even the company’s apology was tinged with disrespect, some noted, with the use of “you guys” and for what it didn’t include.
As Liesl Young, MD, tweeted: “We are not “guys”, we are women. MD = DO. We stand together.”
Dr. Solberg said the apology came across as an apology that feelings were hurt. It should have detailed the changes the company would make to prevent another incident and address the processes that led to the video.
Dr. Solberg said she is seeing something positive come from the whole incident in that, “women are taking up the torch of feminism in such a volatile and divisive time.”
Dr. Solberg reported no relevant financial relationships.
This article first appeared on Medscape.com.
A video that advertised scrubs but denigrated women and DOs has been removed from the company’s website after fierce backlash.
On Tuesday Kevin Klauer, DO, EJD, directed this tweet to the medical uniform company Figs: “@wearfigs REMOVE YOUR DO offensive web ad immediately or the @AOAforDOs will proceed promptly with a defamation lawsuit on behalf of our members and profession.”
Also on Tuesday, the American Association of Colleges of Osteopathic Medicine demanded a public apology.
The video ad featured a woman carrying a “Medical Terminology for Dummies” book upside down while modeling the pink scrubs from all angles and dancing. At one point in the ad, the camera zooms in on the badge clipped to her waistband that read “DO.”
Agnieszka Solberg, MD, a vascular and interventional radiologist and assistant clinical professor at the University of North Dakota in Grand Forks, was among those voicing pointed criticism on social media.
“This was another hit for our DO colleagues,” she said in an interview, emphasizing that MDs and DOs provide the same level of care.
AACOM tweeted: “We are outraged women physicians & doctors of osteopathic medicine are still attacked in ignorant marketing campaigns. A company like @wearfigs should be ashamed for promoting these stereotypes. We demand the respect we’ve earned AND a public apology.”
Dr. Solberg says this is not the first offense by the company. She said she had stopped buying the company’s scrubs a year ago because the ads “have been portraying female providers as dumb and silly. This was the final straw.”
She said the timing of the ad is suspect as DOs had been swept into a storm of negativity earlier this month, as Medscape Medical News reported, when some questioned the qualifications of President Donald Trump’s physician, Sean Conley, who is a DO.
The scrubs ad ignited criticism across specialties, provider levels, and genders.
Jessica K. Willett, MD, tweeted: “As women physicians in 2020, we still struggle to be taken seriously compared to our male counterparts, as we battle stereotypes like THIS EXACT ONE. We expect the brands we support to reflect the badasses we are.”
The company responded to her tweet: “Thank you so much for the feedback! Totally not our intent – we’re taking down both the men’s and women’s versions of this ASAP! I really appreciate you taking the time to share this.”
The company did not respond to a request for comment but issued an apology on social media: “A lot of you guys have pointed out an insensitive video we had on our site – we are incredibly sorry for any hurt this has caused you, especially our female DOs (who are amazing!) FIGS is a female founded company whose only mission is to make you guys feel awesome.”
The Los Angeles–based company, which Forbes estimated will make $250 million in sales this year, was founded by co-CEOs Heather Hasson and Trina Spear.
A med student wrote on Twitter: “As a female and a DO student, how would I ever “feel awesome” about myself knowing that this is how you view me??? And how you want others to view me??? Women and DO’s have fought stereotypes way too long for you to go ahead and put this out there. Do better.”
Even the company’s apology was tinged with disrespect, some noted, with the use of “you guys” and for what it didn’t include.
As Liesl Young, MD, tweeted: “We are not “guys”, we are women. MD = DO. We stand together.”
Dr. Solberg said the apology came across as an apology that feelings were hurt. It should have detailed the changes the company would make to prevent another incident and address the processes that led to the video.
Dr. Solberg said she is seeing something positive come from the whole incident in that, “women are taking up the torch of feminism in such a volatile and divisive time.”
Dr. Solberg reported no relevant financial relationships.
This article first appeared on Medscape.com.
A video that advertised scrubs but denigrated women and DOs has been removed from the company’s website after fierce backlash.
On Tuesday Kevin Klauer, DO, EJD, directed this tweet to the medical uniform company Figs: “@wearfigs REMOVE YOUR DO offensive web ad immediately or the @AOAforDOs will proceed promptly with a defamation lawsuit on behalf of our members and profession.”
Also on Tuesday, the American Association of Colleges of Osteopathic Medicine demanded a public apology.
The video ad featured a woman carrying a “Medical Terminology for Dummies” book upside down while modeling the pink scrubs from all angles and dancing. At one point in the ad, the camera zooms in on the badge clipped to her waistband that read “DO.”
Agnieszka Solberg, MD, a vascular and interventional radiologist and assistant clinical professor at the University of North Dakota in Grand Forks, was among those voicing pointed criticism on social media.
“This was another hit for our DO colleagues,” she said in an interview, emphasizing that MDs and DOs provide the same level of care.
AACOM tweeted: “We are outraged women physicians & doctors of osteopathic medicine are still attacked in ignorant marketing campaigns. A company like @wearfigs should be ashamed for promoting these stereotypes. We demand the respect we’ve earned AND a public apology.”
Dr. Solberg says this is not the first offense by the company. She said she had stopped buying the company’s scrubs a year ago because the ads “have been portraying female providers as dumb and silly. This was the final straw.”
She said the timing of the ad is suspect as DOs had been swept into a storm of negativity earlier this month, as Medscape Medical News reported, when some questioned the qualifications of President Donald Trump’s physician, Sean Conley, who is a DO.
The scrubs ad ignited criticism across specialties, provider levels, and genders.
Jessica K. Willett, MD, tweeted: “As women physicians in 2020, we still struggle to be taken seriously compared to our male counterparts, as we battle stereotypes like THIS EXACT ONE. We expect the brands we support to reflect the badasses we are.”
The company responded to her tweet: “Thank you so much for the feedback! Totally not our intent – we’re taking down both the men’s and women’s versions of this ASAP! I really appreciate you taking the time to share this.”
The company did not respond to a request for comment but issued an apology on social media: “A lot of you guys have pointed out an insensitive video we had on our site – we are incredibly sorry for any hurt this has caused you, especially our female DOs (who are amazing!) FIGS is a female founded company whose only mission is to make you guys feel awesome.”
The Los Angeles–based company, which Forbes estimated will make $250 million in sales this year, was founded by co-CEOs Heather Hasson and Trina Spear.
A med student wrote on Twitter: “As a female and a DO student, how would I ever “feel awesome” about myself knowing that this is how you view me??? And how you want others to view me??? Women and DO’s have fought stereotypes way too long for you to go ahead and put this out there. Do better.”
Even the company’s apology was tinged with disrespect, some noted, with the use of “you guys” and for what it didn’t include.
As Liesl Young, MD, tweeted: “We are not “guys”, we are women. MD = DO. We stand together.”
Dr. Solberg said the apology came across as an apology that feelings were hurt. It should have detailed the changes the company would make to prevent another incident and address the processes that led to the video.
Dr. Solberg said she is seeing something positive come from the whole incident in that, “women are taking up the torch of feminism in such a volatile and divisive time.”
Dr. Solberg reported no relevant financial relationships.
This article first appeared on Medscape.com.
NMOSD challenges in children
, but have led to some uncertainty and confusion as well.
At the2020 CNS-ICNA Conjoint Meeting, held virtually this year, presenters discussed some of the challenges of differential diagnosis and treatment choice in pediatric NMOSD, which is easily confused with multiple sclerosis.
NMOSD used to be considered a monophasic disease restricted to the optic nerve and spinal cord, but is now known to affect other regions of the central nervous system and to relapse in some patients.
Diagnosis
The disease is often mediated by antibodies to the aquaporin-4 (AQP-4) water channel, but about 30% of adult patients lack the antibody, and AQP-4 seronegativity is more common in the pediatric population. Another common antibody found in 40%–50% of children with NMOSD targets myelin oligodendrocyte glycoprotein (MOG).
It is important to be aware that false negatives can occur in serology assays, and false positives are common, particularly in ELISA assays, Silvia N. Tenembaum, MD, said during her presentation. For those reasons, serology is not enough for a diagnosis. “Patients should also have compatible symptoms and MRI findings,” said Dr. Tenembaum, director of the pediatric neuroimmunology program at National Pediatric Hospital in Buenos Aires.
According to international consensus criteria, to be diagnosed with NMOSD, AQP-4 seropositive patients should also have at least one core clinical symptom: optic neuritis, acute myelitis, area postrema syndrome, other acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, or symptomatic cerebral syndrome. AQP-4 seronegative patients or with unknown status should have at least two core symptoms, one of which must be optic neuritis, acute myelitis, or area postrema syndrome. Both conventional MRI and advanced new techniques are important for achieving differential diagnosis.
The most common symptom in children is optic neuritis, which occurs in 50%-70% of patients. Cerebral syndromes with or without encephalopathy and large tumefactive white matter lesions are also common, according to Dr. Tenembaum.
There are many conditions that mimic the spinal cord and optic nerve symptoms of NMOSD, which must be ruled out. One example is optic myelopathy and vision loss from late-onset biotinylase deficiency. It is critical to rule that out because it is treatable with supplements. Optic neuropathy, papillitis, and papilledema can also resemble NMOSD.
It is critical to achieve an early diagnosis of NMOSD in children, because some MS drugs can worsen NMOSD, according to Thaís Armangue, MD, PhD, head of neuroimmunology at SJD Barcelona Children’s Hospital, who also presented at the session. She pointed out that the MOG antibody, while common in children, is also associated with many demyelinating diseases. Some 50%-60% of children with acute disseminated encephalomyelitis (ADEM) have high titers of MOG antibodies. Although early studies suggested that persistent anti-MOG antibodies were associated with risk of developing MS, more recent studies show it predicts a non-MS disease course, particularly at titers greater than 1:1280, according to Dr. Tenembaum. Persistent anti-MOG antibodies are also associated with relapsing disease, but it is associated with other syndromes besides NMOSD. “The probability is that [MOG antibodies are] useful, but they cannot guide chronic immunotherapy, because even monophasic patients can last maybe 12 months before they become MOG negative, and we cannot wait so many months” to determine treatment course, said Dr. Tenembaum.
For monophasic ADEM or NMOSD, there is no need for chronic treatment. But children with MS and recurrent NMOSD require early chronic immunotherapy because specific therapies have been shown to improve prognosis.
Acute treatment
When it comes to acute treatment of NMOSD, the goal is to suppress the inflammatory attack but also to minimize long-term damage and optimize long-term neurological function. “The potential for irreversible injury with an attack is very high, and cumulative disabilities in NMOSD can result directly from attacks,” E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children at the University of Toronto, said during her talk.
IV steroids are generally the first choice, with a preference for methylprednisolone. Pediatric patients that are MOG antibody positive usually respond better and more quickly than do adults, with rapid daily improvements in mobility, vomiting, and eyesight. Dr. Yeh recommends weaning good responders off steroids because AQP-4 positive patients are likely to relapse without a steroid wean, and antibody testing may be unavailable or results may be delayed. The wean can range from 4 weeks to 4-6 months, depending on antibody status, likelihood of AQP-4 positivity, and clinical parameters.
Inadequate responses are usually pretty evident. If there is only light perception by day 4 or 5, or paralyzed patients are nonambulatory and achieve only twitchy movements by that time, second-line therapies should be considered, including therapeutic plasma exchange (TPE) with 5-7 exchanges or intravenous immunoglobulins (IVIg).
Dr. Yeh called for quick treatment. Whatever you do, “please do it sooner rather than later if you think there’s no response [to steroids],” Dr. Yeh said.
TPE is the first choice, according to Dr. Yeh. “There seems to be a fair amount of information that suggests that if you’re having difficulty getting a response to steroids, TPE can make a difference in these patients,” she said. But in some cases TPE may not be available, and IVIg can be attempted first. If it achieves no or only marginal improvement, TPE can be attempted later, but it must be kept in mind that TPE conducted too soon could wash out IVIg. Patients who get much better on IVIg can undergo a steroid wean, and then be evaluated for prophylactic therapy, said Dr. Yeh.
The evidence for IVIg is limited, reflecting the difficulty of studying treatments in rare populations. Still, when TPE is not available and the patient is quite impaired, IVIg makes sense to try. “Absence of evidence does not mean that the therapy doesn’t work, and I don’t think we should throw out the baby with the bath water,” said Dr. Yeh.
Although IVIg treatment is generally well tolerated, there have been a few serious adverse events, such as anaphylactic shock and aseptic meningitis, according to Andrea Savransky, MD, a pediatrician at National Pediatric Hospital in Buenos Aires, who also spoke at the session. “I think it is important to weigh the benefits against the risk,” Dr. Savransky said. She noted that TPE should not be taken lightly. One study showed more complications in pediatric patients than in adult patients, and it must be performed in specialized centers.
Emerging treaments
Tanuja Chitnis, MD, director of the Partners Pediatric MS Center at Massachusetts General Hospital, Boston, discussed some of the emerging treatments for pediatric NMOSD. Rituximab has been associated with success in some retrospective studies, but dosing should be personalized. Dr. Chitnis reported that B cells can return before 6 months, so she monitors B cells beginning 2 months after induction, redosing after 4 or 5 months rather than 6 if B cells return.
Nevertheless, relapses can still occur after rituximab therapy. “There is room for additional therapies to address this gap,” said Dr. Chitnis. Three new antibodies have received approval for treatment of NMOSD in adults. These include the complement inhibitor eculizumab, the IL-6 receptor antibody satralizumab, and the anti-CD19 antibody inebilizumab. Phase 3 clinical trials in children have been conducted for eculizumab and are in the planning stage for inebilizumab, and pediatric patients were included in pivotal trials for satralizumab.
Eculizumab treatment resulted in a 94.2% reduction in relapse risk in AQP4-positive adults. Satralizumab showed a 79% reduction in relapse risk among AQP-4 positive subjects with NMOSD or neuromyelitis optica and a 34% reduction in those who were AQP-4 negative. The pediatric subgroup had similar levels of response to adults, though the numbers were too small for a subgroup analysis.
In AQP-4 positive patients, inebilizumab treatment yielded a 77% reduction in relapse rate. In all patients, there was a 73% reduction.
For MOG antibody-positive patients with AQP-4 negative disease, novel therapies are at earlier stages of development. Typical MS therapies such as interferon beta and glatiramer acetate don’t seem to be effective. Some that have shown signs of efficacy include azathioprine, mycophenylate mofetil, rituximab, and IVIg infusion, but the state of the field is not encouraging. “This is an observation now being studied in larger cohorts, but in general I have not found that there’s a very strong response to any of these therapies, possibly with the exception of IVIg,” said Dr. Chitnis.
Dr. Tenembaum has no relevant financial disclosures. Dr. Armangue has received speaking honoraria from Novartis and travel expenses for scientific meetings from Merck, Biogen, and Roche. Dr. Yeh is on the scientific advisory board of Juno Therapeutics and has received research support from Biogen. Dr. Chitnis advises Biogen-Idec, Novartis, and Alexion, serves on clinical trial advisory boards for Novartis and Sanofi Aventis, and has received research support from Verily, EMD Serono, and Novartis. Dr. Savransky has received honoraria from Genzyme de Argentina SA.
, but have led to some uncertainty and confusion as well.
At the2020 CNS-ICNA Conjoint Meeting, held virtually this year, presenters discussed some of the challenges of differential diagnosis and treatment choice in pediatric NMOSD, which is easily confused with multiple sclerosis.
NMOSD used to be considered a monophasic disease restricted to the optic nerve and spinal cord, but is now known to affect other regions of the central nervous system and to relapse in some patients.
Diagnosis
The disease is often mediated by antibodies to the aquaporin-4 (AQP-4) water channel, but about 30% of adult patients lack the antibody, and AQP-4 seronegativity is more common in the pediatric population. Another common antibody found in 40%–50% of children with NMOSD targets myelin oligodendrocyte glycoprotein (MOG).
It is important to be aware that false negatives can occur in serology assays, and false positives are common, particularly in ELISA assays, Silvia N. Tenembaum, MD, said during her presentation. For those reasons, serology is not enough for a diagnosis. “Patients should also have compatible symptoms and MRI findings,” said Dr. Tenembaum, director of the pediatric neuroimmunology program at National Pediatric Hospital in Buenos Aires.
According to international consensus criteria, to be diagnosed with NMOSD, AQP-4 seropositive patients should also have at least one core clinical symptom: optic neuritis, acute myelitis, area postrema syndrome, other acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, or symptomatic cerebral syndrome. AQP-4 seronegative patients or with unknown status should have at least two core symptoms, one of which must be optic neuritis, acute myelitis, or area postrema syndrome. Both conventional MRI and advanced new techniques are important for achieving differential diagnosis.
The most common symptom in children is optic neuritis, which occurs in 50%-70% of patients. Cerebral syndromes with or without encephalopathy and large tumefactive white matter lesions are also common, according to Dr. Tenembaum.
There are many conditions that mimic the spinal cord and optic nerve symptoms of NMOSD, which must be ruled out. One example is optic myelopathy and vision loss from late-onset biotinylase deficiency. It is critical to rule that out because it is treatable with supplements. Optic neuropathy, papillitis, and papilledema can also resemble NMOSD.
It is critical to achieve an early diagnosis of NMOSD in children, because some MS drugs can worsen NMOSD, according to Thaís Armangue, MD, PhD, head of neuroimmunology at SJD Barcelona Children’s Hospital, who also presented at the session. She pointed out that the MOG antibody, while common in children, is also associated with many demyelinating diseases. Some 50%-60% of children with acute disseminated encephalomyelitis (ADEM) have high titers of MOG antibodies. Although early studies suggested that persistent anti-MOG antibodies were associated with risk of developing MS, more recent studies show it predicts a non-MS disease course, particularly at titers greater than 1:1280, according to Dr. Tenembaum. Persistent anti-MOG antibodies are also associated with relapsing disease, but it is associated with other syndromes besides NMOSD. “The probability is that [MOG antibodies are] useful, but they cannot guide chronic immunotherapy, because even monophasic patients can last maybe 12 months before they become MOG negative, and we cannot wait so many months” to determine treatment course, said Dr. Tenembaum.
For monophasic ADEM or NMOSD, there is no need for chronic treatment. But children with MS and recurrent NMOSD require early chronic immunotherapy because specific therapies have been shown to improve prognosis.
Acute treatment
When it comes to acute treatment of NMOSD, the goal is to suppress the inflammatory attack but also to minimize long-term damage and optimize long-term neurological function. “The potential for irreversible injury with an attack is very high, and cumulative disabilities in NMOSD can result directly from attacks,” E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children at the University of Toronto, said during her talk.
IV steroids are generally the first choice, with a preference for methylprednisolone. Pediatric patients that are MOG antibody positive usually respond better and more quickly than do adults, with rapid daily improvements in mobility, vomiting, and eyesight. Dr. Yeh recommends weaning good responders off steroids because AQP-4 positive patients are likely to relapse without a steroid wean, and antibody testing may be unavailable or results may be delayed. The wean can range from 4 weeks to 4-6 months, depending on antibody status, likelihood of AQP-4 positivity, and clinical parameters.
Inadequate responses are usually pretty evident. If there is only light perception by day 4 or 5, or paralyzed patients are nonambulatory and achieve only twitchy movements by that time, second-line therapies should be considered, including therapeutic plasma exchange (TPE) with 5-7 exchanges or intravenous immunoglobulins (IVIg).
Dr. Yeh called for quick treatment. Whatever you do, “please do it sooner rather than later if you think there’s no response [to steroids],” Dr. Yeh said.
TPE is the first choice, according to Dr. Yeh. “There seems to be a fair amount of information that suggests that if you’re having difficulty getting a response to steroids, TPE can make a difference in these patients,” she said. But in some cases TPE may not be available, and IVIg can be attempted first. If it achieves no or only marginal improvement, TPE can be attempted later, but it must be kept in mind that TPE conducted too soon could wash out IVIg. Patients who get much better on IVIg can undergo a steroid wean, and then be evaluated for prophylactic therapy, said Dr. Yeh.
The evidence for IVIg is limited, reflecting the difficulty of studying treatments in rare populations. Still, when TPE is not available and the patient is quite impaired, IVIg makes sense to try. “Absence of evidence does not mean that the therapy doesn’t work, and I don’t think we should throw out the baby with the bath water,” said Dr. Yeh.
Although IVIg treatment is generally well tolerated, there have been a few serious adverse events, such as anaphylactic shock and aseptic meningitis, according to Andrea Savransky, MD, a pediatrician at National Pediatric Hospital in Buenos Aires, who also spoke at the session. “I think it is important to weigh the benefits against the risk,” Dr. Savransky said. She noted that TPE should not be taken lightly. One study showed more complications in pediatric patients than in adult patients, and it must be performed in specialized centers.
Emerging treaments
Tanuja Chitnis, MD, director of the Partners Pediatric MS Center at Massachusetts General Hospital, Boston, discussed some of the emerging treatments for pediatric NMOSD. Rituximab has been associated with success in some retrospective studies, but dosing should be personalized. Dr. Chitnis reported that B cells can return before 6 months, so she monitors B cells beginning 2 months after induction, redosing after 4 or 5 months rather than 6 if B cells return.
Nevertheless, relapses can still occur after rituximab therapy. “There is room for additional therapies to address this gap,” said Dr. Chitnis. Three new antibodies have received approval for treatment of NMOSD in adults. These include the complement inhibitor eculizumab, the IL-6 receptor antibody satralizumab, and the anti-CD19 antibody inebilizumab. Phase 3 clinical trials in children have been conducted for eculizumab and are in the planning stage for inebilizumab, and pediatric patients were included in pivotal trials for satralizumab.
Eculizumab treatment resulted in a 94.2% reduction in relapse risk in AQP4-positive adults. Satralizumab showed a 79% reduction in relapse risk among AQP-4 positive subjects with NMOSD or neuromyelitis optica and a 34% reduction in those who were AQP-4 negative. The pediatric subgroup had similar levels of response to adults, though the numbers were too small for a subgroup analysis.
In AQP-4 positive patients, inebilizumab treatment yielded a 77% reduction in relapse rate. In all patients, there was a 73% reduction.
For MOG antibody-positive patients with AQP-4 negative disease, novel therapies are at earlier stages of development. Typical MS therapies such as interferon beta and glatiramer acetate don’t seem to be effective. Some that have shown signs of efficacy include azathioprine, mycophenylate mofetil, rituximab, and IVIg infusion, but the state of the field is not encouraging. “This is an observation now being studied in larger cohorts, but in general I have not found that there’s a very strong response to any of these therapies, possibly with the exception of IVIg,” said Dr. Chitnis.
Dr. Tenembaum has no relevant financial disclosures. Dr. Armangue has received speaking honoraria from Novartis and travel expenses for scientific meetings from Merck, Biogen, and Roche. Dr. Yeh is on the scientific advisory board of Juno Therapeutics and has received research support from Biogen. Dr. Chitnis advises Biogen-Idec, Novartis, and Alexion, serves on clinical trial advisory boards for Novartis and Sanofi Aventis, and has received research support from Verily, EMD Serono, and Novartis. Dr. Savransky has received honoraria from Genzyme de Argentina SA.
, but have led to some uncertainty and confusion as well.
At the2020 CNS-ICNA Conjoint Meeting, held virtually this year, presenters discussed some of the challenges of differential diagnosis and treatment choice in pediatric NMOSD, which is easily confused with multiple sclerosis.
NMOSD used to be considered a monophasic disease restricted to the optic nerve and spinal cord, but is now known to affect other regions of the central nervous system and to relapse in some patients.
Diagnosis
The disease is often mediated by antibodies to the aquaporin-4 (AQP-4) water channel, but about 30% of adult patients lack the antibody, and AQP-4 seronegativity is more common in the pediatric population. Another common antibody found in 40%–50% of children with NMOSD targets myelin oligodendrocyte glycoprotein (MOG).
It is important to be aware that false negatives can occur in serology assays, and false positives are common, particularly in ELISA assays, Silvia N. Tenembaum, MD, said during her presentation. For those reasons, serology is not enough for a diagnosis. “Patients should also have compatible symptoms and MRI findings,” said Dr. Tenembaum, director of the pediatric neuroimmunology program at National Pediatric Hospital in Buenos Aires.
According to international consensus criteria, to be diagnosed with NMOSD, AQP-4 seropositive patients should also have at least one core clinical symptom: optic neuritis, acute myelitis, area postrema syndrome, other acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, or symptomatic cerebral syndrome. AQP-4 seronegative patients or with unknown status should have at least two core symptoms, one of which must be optic neuritis, acute myelitis, or area postrema syndrome. Both conventional MRI and advanced new techniques are important for achieving differential diagnosis.
The most common symptom in children is optic neuritis, which occurs in 50%-70% of patients. Cerebral syndromes with or without encephalopathy and large tumefactive white matter lesions are also common, according to Dr. Tenembaum.
There are many conditions that mimic the spinal cord and optic nerve symptoms of NMOSD, which must be ruled out. One example is optic myelopathy and vision loss from late-onset biotinylase deficiency. It is critical to rule that out because it is treatable with supplements. Optic neuropathy, papillitis, and papilledema can also resemble NMOSD.
It is critical to achieve an early diagnosis of NMOSD in children, because some MS drugs can worsen NMOSD, according to Thaís Armangue, MD, PhD, head of neuroimmunology at SJD Barcelona Children’s Hospital, who also presented at the session. She pointed out that the MOG antibody, while common in children, is also associated with many demyelinating diseases. Some 50%-60% of children with acute disseminated encephalomyelitis (ADEM) have high titers of MOG antibodies. Although early studies suggested that persistent anti-MOG antibodies were associated with risk of developing MS, more recent studies show it predicts a non-MS disease course, particularly at titers greater than 1:1280, according to Dr. Tenembaum. Persistent anti-MOG antibodies are also associated with relapsing disease, but it is associated with other syndromes besides NMOSD. “The probability is that [MOG antibodies are] useful, but they cannot guide chronic immunotherapy, because even monophasic patients can last maybe 12 months before they become MOG negative, and we cannot wait so many months” to determine treatment course, said Dr. Tenembaum.
For monophasic ADEM or NMOSD, there is no need for chronic treatment. But children with MS and recurrent NMOSD require early chronic immunotherapy because specific therapies have been shown to improve prognosis.
Acute treatment
When it comes to acute treatment of NMOSD, the goal is to suppress the inflammatory attack but also to minimize long-term damage and optimize long-term neurological function. “The potential for irreversible injury with an attack is very high, and cumulative disabilities in NMOSD can result directly from attacks,” E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children at the University of Toronto, said during her talk.
IV steroids are generally the first choice, with a preference for methylprednisolone. Pediatric patients that are MOG antibody positive usually respond better and more quickly than do adults, with rapid daily improvements in mobility, vomiting, and eyesight. Dr. Yeh recommends weaning good responders off steroids because AQP-4 positive patients are likely to relapse without a steroid wean, and antibody testing may be unavailable or results may be delayed. The wean can range from 4 weeks to 4-6 months, depending on antibody status, likelihood of AQP-4 positivity, and clinical parameters.
Inadequate responses are usually pretty evident. If there is only light perception by day 4 or 5, or paralyzed patients are nonambulatory and achieve only twitchy movements by that time, second-line therapies should be considered, including therapeutic plasma exchange (TPE) with 5-7 exchanges or intravenous immunoglobulins (IVIg).
Dr. Yeh called for quick treatment. Whatever you do, “please do it sooner rather than later if you think there’s no response [to steroids],” Dr. Yeh said.
TPE is the first choice, according to Dr. Yeh. “There seems to be a fair amount of information that suggests that if you’re having difficulty getting a response to steroids, TPE can make a difference in these patients,” she said. But in some cases TPE may not be available, and IVIg can be attempted first. If it achieves no or only marginal improvement, TPE can be attempted later, but it must be kept in mind that TPE conducted too soon could wash out IVIg. Patients who get much better on IVIg can undergo a steroid wean, and then be evaluated for prophylactic therapy, said Dr. Yeh.
The evidence for IVIg is limited, reflecting the difficulty of studying treatments in rare populations. Still, when TPE is not available and the patient is quite impaired, IVIg makes sense to try. “Absence of evidence does not mean that the therapy doesn’t work, and I don’t think we should throw out the baby with the bath water,” said Dr. Yeh.
Although IVIg treatment is generally well tolerated, there have been a few serious adverse events, such as anaphylactic shock and aseptic meningitis, according to Andrea Savransky, MD, a pediatrician at National Pediatric Hospital in Buenos Aires, who also spoke at the session. “I think it is important to weigh the benefits against the risk,” Dr. Savransky said. She noted that TPE should not be taken lightly. One study showed more complications in pediatric patients than in adult patients, and it must be performed in specialized centers.
Emerging treaments
Tanuja Chitnis, MD, director of the Partners Pediatric MS Center at Massachusetts General Hospital, Boston, discussed some of the emerging treatments for pediatric NMOSD. Rituximab has been associated with success in some retrospective studies, but dosing should be personalized. Dr. Chitnis reported that B cells can return before 6 months, so she monitors B cells beginning 2 months after induction, redosing after 4 or 5 months rather than 6 if B cells return.
Nevertheless, relapses can still occur after rituximab therapy. “There is room for additional therapies to address this gap,” said Dr. Chitnis. Three new antibodies have received approval for treatment of NMOSD in adults. These include the complement inhibitor eculizumab, the IL-6 receptor antibody satralizumab, and the anti-CD19 antibody inebilizumab. Phase 3 clinical trials in children have been conducted for eculizumab and are in the planning stage for inebilizumab, and pediatric patients were included in pivotal trials for satralizumab.
Eculizumab treatment resulted in a 94.2% reduction in relapse risk in AQP4-positive adults. Satralizumab showed a 79% reduction in relapse risk among AQP-4 positive subjects with NMOSD or neuromyelitis optica and a 34% reduction in those who were AQP-4 negative. The pediatric subgroup had similar levels of response to adults, though the numbers were too small for a subgroup analysis.
In AQP-4 positive patients, inebilizumab treatment yielded a 77% reduction in relapse rate. In all patients, there was a 73% reduction.
For MOG antibody-positive patients with AQP-4 negative disease, novel therapies are at earlier stages of development. Typical MS therapies such as interferon beta and glatiramer acetate don’t seem to be effective. Some that have shown signs of efficacy include azathioprine, mycophenylate mofetil, rituximab, and IVIg infusion, but the state of the field is not encouraging. “This is an observation now being studied in larger cohorts, but in general I have not found that there’s a very strong response to any of these therapies, possibly with the exception of IVIg,” said Dr. Chitnis.
Dr. Tenembaum has no relevant financial disclosures. Dr. Armangue has received speaking honoraria from Novartis and travel expenses for scientific meetings from Merck, Biogen, and Roche. Dr. Yeh is on the scientific advisory board of Juno Therapeutics and has received research support from Biogen. Dr. Chitnis advises Biogen-Idec, Novartis, and Alexion, serves on clinical trial advisory boards for Novartis and Sanofi Aventis, and has received research support from Verily, EMD Serono, and Novartis. Dr. Savransky has received honoraria from Genzyme de Argentina SA.
FROM CNS-ICNA 2020
Worldwide measles vaccination is flagging
After almost 2 decades of progress, the global state of measles vaccination and measles mortality is deteriorating.
One of the most serious concerns of measles infection is its long-term neurological complications, including the fatal subacute sclerosing panencephalitis (SSPE) and measles inclusion-body encephalitis (MIBE), which is usually seen in immune deficient children. Although some efforts are being made to determine which patients might be most vulnerable to these outcomes, and to treat them, the best approach is still prevention and vaccination, according to Banu Anlar, MD, of Hacettepe University, Ankara, Turkey, who spoke during a session at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
Worldwide vaccination strategies have slipped in recent years, leading to upticks in measles cases and vaccination rates. As a result, in 2018 the World Health Organization postponed its goal of eliminating measles by 2020. Future eradication goals will likely need to be modified, according to Anaita Udwadia Hegde MD, a pediatric neurologist in Mumbai, India, who also presented at the session.
After measles deaths dropped 74% between 2000 and 2010, coinciding with widespread increases in vaccination, the WHO felt emboldened to deal the disease a knockout blow. In 2010, it held a Global Technical Consultation to determine the feasibility of an eradication campaign, which concluded it should be possible by 2020. Several characteristics of measles made that a reasonable goal: It is passed only among humans, with no known animal reservoir; natural infection grants lifelong immunity; there is only one serotype; the virus is genetically stable; the vaccine is safe and leads to 95%-97% seroconversion after two doses, which provides long-term protection against known genotypes; the disease is easily recognized and tested for; and it had been successfully eliminated already in some regions of the world.
As of 2017, analyses showed that the vaccination program saved the lives of about 1.5 million children. That was a cause for celebration, but the goal of eradication has remained elusive. Vaccination rates have trailed targets. In 2018, UNICEF and WHO estimated that 86% of children globally received the first measles vaccine, unchanged from 2010 and below the goal of 95%. Only 69% of children received the second dose, below the goal of 80%. Four countries in Europe lost their measles elimination status in 2018.
Other attempts to eradicate diseases have met with mixed results. The only full success was smallpox, eliminated in 1977. Similar efforts with polio, malaria, guinea worm, and now measles have all come up short. Those failures could complicate future efforts because global agencies and donors may be leery of past failures because of potential harm to their reputations, according to Dr. Hegde.
Such programs require sustained financial commitment and political support as well as local trust. Nevertheless, they must continue for ethical reasons, said Dr. Hegde, but also for economic ones: Every $1 spent on vaccination programs saves $58 in future costs in low- and middle-income countries. Missed childhood vaccination also results in future vulnerable teenagers and young adults, and these populations are much harder to reach and can drive large outbreaks.
Several factors are contributing to the global regression in vaccine coverage, according to Kristen Feemster, MD, MPH, a pediatric infectious disease physician and the global director of medical affairs at Merck. Globalization has enabled the spread of the disease. Most cases in the United States are imported by travelers to countries where the disease is endemic. “Measles can happen anywhere in the world, and when it does it can travel and spread. If you have an unvaccinated traveler who is exposed to measles abroad, they can return home and spread it to anyone else who is unvaccinated or not otherwise immune. When we see cases they’ve been sporadic, but if you return to a community where immunization rates are low, you have the potential for more sustained spread,” Dr. Feemster said during her presentation.
Why are so many travelers unvaccinated? A key reason is that vaccine hesitance is growing. Most affected individuals involved in outbreaks are unvaccinated, usually by choice rather than for medical reasons. Concerns continue over the measles vaccine and autism, growing out of the debunked studies of Andrew Wakefield. In one example, a Somali community in Minnesota experienced a higher than usual number of autism cases and parents sought reasons to explain it. They discovered the supposed connection between vaccination and autism, and Wakefield himself met with a group of them. The result was a drop in vaccination and, in 2011 and 2017, sizable measles outbreaks.
2020 has of course brought a fresh challenge to measles vaccine with the COVID-19 pandemic, which has reduced access to health care and shifted scientific and health care interest away from measles and other vaccine-preventable diseases. On the positive side, social distancing, mask wearing, and restricted movement are likely reducing exposure to measles, but reduced vaccination rates are likely to result in future outbreaks. “There’s been a significant decrease in rates for routine immunizations globally, so there’s a potential for yet another resurgence of measles and other vaccine-preventable diseases,” said Dr. Feemster.
Dr. Feemster is an employee of Merck. Dr. Anlar and Dr. Hegde did not disclose any relevant financial relationships.
After almost 2 decades of progress, the global state of measles vaccination and measles mortality is deteriorating.
One of the most serious concerns of measles infection is its long-term neurological complications, including the fatal subacute sclerosing panencephalitis (SSPE) and measles inclusion-body encephalitis (MIBE), which is usually seen in immune deficient children. Although some efforts are being made to determine which patients might be most vulnerable to these outcomes, and to treat them, the best approach is still prevention and vaccination, according to Banu Anlar, MD, of Hacettepe University, Ankara, Turkey, who spoke during a session at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
Worldwide vaccination strategies have slipped in recent years, leading to upticks in measles cases and vaccination rates. As a result, in 2018 the World Health Organization postponed its goal of eliminating measles by 2020. Future eradication goals will likely need to be modified, according to Anaita Udwadia Hegde MD, a pediatric neurologist in Mumbai, India, who also presented at the session.
After measles deaths dropped 74% between 2000 and 2010, coinciding with widespread increases in vaccination, the WHO felt emboldened to deal the disease a knockout blow. In 2010, it held a Global Technical Consultation to determine the feasibility of an eradication campaign, which concluded it should be possible by 2020. Several characteristics of measles made that a reasonable goal: It is passed only among humans, with no known animal reservoir; natural infection grants lifelong immunity; there is only one serotype; the virus is genetically stable; the vaccine is safe and leads to 95%-97% seroconversion after two doses, which provides long-term protection against known genotypes; the disease is easily recognized and tested for; and it had been successfully eliminated already in some regions of the world.
As of 2017, analyses showed that the vaccination program saved the lives of about 1.5 million children. That was a cause for celebration, but the goal of eradication has remained elusive. Vaccination rates have trailed targets. In 2018, UNICEF and WHO estimated that 86% of children globally received the first measles vaccine, unchanged from 2010 and below the goal of 95%. Only 69% of children received the second dose, below the goal of 80%. Four countries in Europe lost their measles elimination status in 2018.
Other attempts to eradicate diseases have met with mixed results. The only full success was smallpox, eliminated in 1977. Similar efforts with polio, malaria, guinea worm, and now measles have all come up short. Those failures could complicate future efforts because global agencies and donors may be leery of past failures because of potential harm to their reputations, according to Dr. Hegde.
Such programs require sustained financial commitment and political support as well as local trust. Nevertheless, they must continue for ethical reasons, said Dr. Hegde, but also for economic ones: Every $1 spent on vaccination programs saves $58 in future costs in low- and middle-income countries. Missed childhood vaccination also results in future vulnerable teenagers and young adults, and these populations are much harder to reach and can drive large outbreaks.
Several factors are contributing to the global regression in vaccine coverage, according to Kristen Feemster, MD, MPH, a pediatric infectious disease physician and the global director of medical affairs at Merck. Globalization has enabled the spread of the disease. Most cases in the United States are imported by travelers to countries where the disease is endemic. “Measles can happen anywhere in the world, and when it does it can travel and spread. If you have an unvaccinated traveler who is exposed to measles abroad, they can return home and spread it to anyone else who is unvaccinated or not otherwise immune. When we see cases they’ve been sporadic, but if you return to a community where immunization rates are low, you have the potential for more sustained spread,” Dr. Feemster said during her presentation.
Why are so many travelers unvaccinated? A key reason is that vaccine hesitance is growing. Most affected individuals involved in outbreaks are unvaccinated, usually by choice rather than for medical reasons. Concerns continue over the measles vaccine and autism, growing out of the debunked studies of Andrew Wakefield. In one example, a Somali community in Minnesota experienced a higher than usual number of autism cases and parents sought reasons to explain it. They discovered the supposed connection between vaccination and autism, and Wakefield himself met with a group of them. The result was a drop in vaccination and, in 2011 and 2017, sizable measles outbreaks.
2020 has of course brought a fresh challenge to measles vaccine with the COVID-19 pandemic, which has reduced access to health care and shifted scientific and health care interest away from measles and other vaccine-preventable diseases. On the positive side, social distancing, mask wearing, and restricted movement are likely reducing exposure to measles, but reduced vaccination rates are likely to result in future outbreaks. “There’s been a significant decrease in rates for routine immunizations globally, so there’s a potential for yet another resurgence of measles and other vaccine-preventable diseases,” said Dr. Feemster.
Dr. Feemster is an employee of Merck. Dr. Anlar and Dr. Hegde did not disclose any relevant financial relationships.
After almost 2 decades of progress, the global state of measles vaccination and measles mortality is deteriorating.
One of the most serious concerns of measles infection is its long-term neurological complications, including the fatal subacute sclerosing panencephalitis (SSPE) and measles inclusion-body encephalitis (MIBE), which is usually seen in immune deficient children. Although some efforts are being made to determine which patients might be most vulnerable to these outcomes, and to treat them, the best approach is still prevention and vaccination, according to Banu Anlar, MD, of Hacettepe University, Ankara, Turkey, who spoke during a session at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
Worldwide vaccination strategies have slipped in recent years, leading to upticks in measles cases and vaccination rates. As a result, in 2018 the World Health Organization postponed its goal of eliminating measles by 2020. Future eradication goals will likely need to be modified, according to Anaita Udwadia Hegde MD, a pediatric neurologist in Mumbai, India, who also presented at the session.
After measles deaths dropped 74% between 2000 and 2010, coinciding with widespread increases in vaccination, the WHO felt emboldened to deal the disease a knockout blow. In 2010, it held a Global Technical Consultation to determine the feasibility of an eradication campaign, which concluded it should be possible by 2020. Several characteristics of measles made that a reasonable goal: It is passed only among humans, with no known animal reservoir; natural infection grants lifelong immunity; there is only one serotype; the virus is genetically stable; the vaccine is safe and leads to 95%-97% seroconversion after two doses, which provides long-term protection against known genotypes; the disease is easily recognized and tested for; and it had been successfully eliminated already in some regions of the world.
As of 2017, analyses showed that the vaccination program saved the lives of about 1.5 million children. That was a cause for celebration, but the goal of eradication has remained elusive. Vaccination rates have trailed targets. In 2018, UNICEF and WHO estimated that 86% of children globally received the first measles vaccine, unchanged from 2010 and below the goal of 95%. Only 69% of children received the second dose, below the goal of 80%. Four countries in Europe lost their measles elimination status in 2018.
Other attempts to eradicate diseases have met with mixed results. The only full success was smallpox, eliminated in 1977. Similar efforts with polio, malaria, guinea worm, and now measles have all come up short. Those failures could complicate future efforts because global agencies and donors may be leery of past failures because of potential harm to their reputations, according to Dr. Hegde.
Such programs require sustained financial commitment and political support as well as local trust. Nevertheless, they must continue for ethical reasons, said Dr. Hegde, but also for economic ones: Every $1 spent on vaccination programs saves $58 in future costs in low- and middle-income countries. Missed childhood vaccination also results in future vulnerable teenagers and young adults, and these populations are much harder to reach and can drive large outbreaks.
Several factors are contributing to the global regression in vaccine coverage, according to Kristen Feemster, MD, MPH, a pediatric infectious disease physician and the global director of medical affairs at Merck. Globalization has enabled the spread of the disease. Most cases in the United States are imported by travelers to countries where the disease is endemic. “Measles can happen anywhere in the world, and when it does it can travel and spread. If you have an unvaccinated traveler who is exposed to measles abroad, they can return home and spread it to anyone else who is unvaccinated or not otherwise immune. When we see cases they’ve been sporadic, but if you return to a community where immunization rates are low, you have the potential for more sustained spread,” Dr. Feemster said during her presentation.
Why are so many travelers unvaccinated? A key reason is that vaccine hesitance is growing. Most affected individuals involved in outbreaks are unvaccinated, usually by choice rather than for medical reasons. Concerns continue over the measles vaccine and autism, growing out of the debunked studies of Andrew Wakefield. In one example, a Somali community in Minnesota experienced a higher than usual number of autism cases and parents sought reasons to explain it. They discovered the supposed connection between vaccination and autism, and Wakefield himself met with a group of them. The result was a drop in vaccination and, in 2011 and 2017, sizable measles outbreaks.
2020 has of course brought a fresh challenge to measles vaccine with the COVID-19 pandemic, which has reduced access to health care and shifted scientific and health care interest away from measles and other vaccine-preventable diseases. On the positive side, social distancing, mask wearing, and restricted movement are likely reducing exposure to measles, but reduced vaccination rates are likely to result in future outbreaks. “There’s been a significant decrease in rates for routine immunizations globally, so there’s a potential for yet another resurgence of measles and other vaccine-preventable diseases,” said Dr. Feemster.
Dr. Feemster is an employee of Merck. Dr. Anlar and Dr. Hegde did not disclose any relevant financial relationships.
FROM CNS-ICNA 2020
Latest week brings 44,000 more children with COVID-19
in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.
Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.
California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.
Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.
Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.
California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.
Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.
Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.
California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.
Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
COVID-19 antibody response not reduced with diabetes
Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.
Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.
Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.
Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.
And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.
This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.
“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
Diabetes and hyperglycemia worsen COVID-19 outcomes
The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.
Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.
Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.
Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.
In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
Antibody response similar in patients with and without diabetes
The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.
After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).
“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).
These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.
They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”
“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”
“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.
The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.
Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.
Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.
Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.
And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.
This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.
“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
Diabetes and hyperglycemia worsen COVID-19 outcomes
The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.
Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.
Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.
Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.
In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
Antibody response similar in patients with and without diabetes
The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.
After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).
“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).
These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.
They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”
“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”
“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.
The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.
Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.
Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.
Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.
And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.
This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.
“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
Diabetes and hyperglycemia worsen COVID-19 outcomes
The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.
Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.
Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.
Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.
In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
Antibody response similar in patients with and without diabetes
The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.
After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).
“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).
These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.
They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”
“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”
“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.
The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Older age, r/r disease in lymphoma patients tied to increased COVID-19 death rate
Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.
Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.
These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.
The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
Promising results for many
There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.
With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.
The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).
Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.
“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.
The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.
SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.
Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.
Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.
These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.
The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
Promising results for many
There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.
With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.
The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).
Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.
“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.
The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.
SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.
Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.
Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.
These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.
The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
Promising results for many
There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.
With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.
The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).
Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.
“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.
The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.
SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.
FROM ECLINICALMEDICINE
Link between vitamin D and ICU outcomes unclear
We can “stop putting money on vitamin D” to help patients who require critical care, said Todd Rice, MD, FCCP.
“Results from vitamin D trials have not been uniformly one way, but they have been pretty uniformly disappointing,” Dr. Rice, from Vanderbilt University Medical Center, Nashville, Tenn., reported at the annual meeting of the American College of Chest Physicians.
Low levels of vitamin D in critically ill COVID-19 patients have been reported in numerous recent studies, and researchers are looking for ways to boost those levels and improve outcomes.
We are seeing “the exact same story” in the critically ill COVID-19 population as we see in the general ICU population, said Dr. Rice. “The whole scenario is repeating itself. I’m pessimistic.”
Still, vitamin D levels can be elevated so, in theory, “the concept makes sense,” he said. There is evidence that, “when given enterally, the levels rise nicely” and vitamin D is absorbed reasonably well.” But is that enough?
When patients are admitted to the ICU, some biomarkers in the body are too high and others are too low. Vitamin D is often too low. So far, though, “supplementing vitamin D in the ICU has not significantly improved outcomes,” said Dr. Rice.
In the Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) trial, Dr. Rice and colleagues found no statistical benefit when a 540,000 IU boost of vitamin D was administered to 2,624 critically ill patients, as reported by Medscape Medical News.
“Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other nonfatal outcomes among critically ill, vitamin D–deficient patients,” the researchers write in their recent report.
In fact, VIOLET ended before enrollment had reached the planned 3,000-patient cohort because the statistical analysis clearly did not show benefit. Those enrolled were in the ICU because of, among other things, pneumonia, sepsis, the need for mechanical ventilation or vasopressors, and risk for acute respiratory distress syndrome.
“It doesn’t look like vitamin D is going to be the answer to our critical care problems,” Dr. Rice said in an interview.
Maintenance dose needed?
One theory suggests that VIOLET might have failed because a maintenance dose is needed after the initial boost of vitamin D.
In the ongoing VITDALIZE trial, critically ill patients with severe vitamin D deficiency (12 ng/mL or less at admission) receive an initial 540,000-IU dose followed by 4,000 IU per day.
The highly anticipated VITDALIZE results are expected in the middle of next year, Dr. Rice reported, so “let’s wait to see.”
“Vitamin D may not have an acute effect,” he theorized. “We can raise your levels, but that doesn’t give you all the benefits of having a sufficient level for a long period of time.”
Another theory suggests that a low level of vitamin D is simply a signal of the severity of disease, not a direct influence on disease pathology.
Some observational data have shown an association between low levels of vitamin D and outcomes in COVID-19 patients (Nutrients. 2020 May 9;12[5]:1359; medRxiv 2020 Apr 24. doi: 10.1101/2020.04.24.20075838; JAMA Netw Open. 2020;3[9]:e2019722; FEBS J. 2020 Jul 23;10.1111/febs.15495; Clin Endocrinol [Oxf]. 2020 Jul 3;10.1111/cen.14276), but some have shown no association (medRxiv. 2020 Jun 26. doi: 10.1101/2020.06.26.20140921; J Public Health [Oxf]. 2020 Aug 18;42[3]:451-60).
Dr. Rice conducted a search of Clinicaltrials.gov immediately before his presentation on Sunday, and found 41 ongoing interventional studies – “not observational studies” – looking at COVID-19 and vitamin D.
“They’re recruiting, they’re enrolling; hopefully we’ll have data soon,” he said.
Researchers have checked a lot of boxes with a resounding yes on the vitamin D question, so there’s reason to think an association does exist for ICU patients, whether or not they have COVID-19.
“Is there a theoretical benefit of vitamin D in the ICU?” Dr. Rice asked. “Yes. Is vitamin D deficient in patients in the ICU? Yes. Is that deficiency associated with poor outcomes? Yes. Can it be replaced safely? Yes.”
However, “we’re not really sure that it improves outcomes,” he said.
A chronic issue?
“Do you think it’s really an issue of the patients being critically ill with vitamin D,” or is it “a chronic issue of having low vitamin D?” asked session moderator Antine Stenbit, MD, PhD, from the University of California, San Diego.
“We don’t know for sure,” Dr. Rice said. Vitamin D might not have a lot of acute effects; it might have effects that are chronic, that work with levels over a period of time, he explained.
“It’s not clear we can correct that with a single dose or with a few days of giving a level that is adequate,” he acknowledged.
Dr. Rice is an investigator in the PETAL network. Dr. Stenbit disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
We can “stop putting money on vitamin D” to help patients who require critical care, said Todd Rice, MD, FCCP.
“Results from vitamin D trials have not been uniformly one way, but they have been pretty uniformly disappointing,” Dr. Rice, from Vanderbilt University Medical Center, Nashville, Tenn., reported at the annual meeting of the American College of Chest Physicians.
Low levels of vitamin D in critically ill COVID-19 patients have been reported in numerous recent studies, and researchers are looking for ways to boost those levels and improve outcomes.
We are seeing “the exact same story” in the critically ill COVID-19 population as we see in the general ICU population, said Dr. Rice. “The whole scenario is repeating itself. I’m pessimistic.”
Still, vitamin D levels can be elevated so, in theory, “the concept makes sense,” he said. There is evidence that, “when given enterally, the levels rise nicely” and vitamin D is absorbed reasonably well.” But is that enough?
When patients are admitted to the ICU, some biomarkers in the body are too high and others are too low. Vitamin D is often too low. So far, though, “supplementing vitamin D in the ICU has not significantly improved outcomes,” said Dr. Rice.
In the Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) trial, Dr. Rice and colleagues found no statistical benefit when a 540,000 IU boost of vitamin D was administered to 2,624 critically ill patients, as reported by Medscape Medical News.
“Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other nonfatal outcomes among critically ill, vitamin D–deficient patients,” the researchers write in their recent report.
In fact, VIOLET ended before enrollment had reached the planned 3,000-patient cohort because the statistical analysis clearly did not show benefit. Those enrolled were in the ICU because of, among other things, pneumonia, sepsis, the need for mechanical ventilation or vasopressors, and risk for acute respiratory distress syndrome.
“It doesn’t look like vitamin D is going to be the answer to our critical care problems,” Dr. Rice said in an interview.
Maintenance dose needed?
One theory suggests that VIOLET might have failed because a maintenance dose is needed after the initial boost of vitamin D.
In the ongoing VITDALIZE trial, critically ill patients with severe vitamin D deficiency (12 ng/mL or less at admission) receive an initial 540,000-IU dose followed by 4,000 IU per day.
The highly anticipated VITDALIZE results are expected in the middle of next year, Dr. Rice reported, so “let’s wait to see.”
“Vitamin D may not have an acute effect,” he theorized. “We can raise your levels, but that doesn’t give you all the benefits of having a sufficient level for a long period of time.”
Another theory suggests that a low level of vitamin D is simply a signal of the severity of disease, not a direct influence on disease pathology.
Some observational data have shown an association between low levels of vitamin D and outcomes in COVID-19 patients (Nutrients. 2020 May 9;12[5]:1359; medRxiv 2020 Apr 24. doi: 10.1101/2020.04.24.20075838; JAMA Netw Open. 2020;3[9]:e2019722; FEBS J. 2020 Jul 23;10.1111/febs.15495; Clin Endocrinol [Oxf]. 2020 Jul 3;10.1111/cen.14276), but some have shown no association (medRxiv. 2020 Jun 26. doi: 10.1101/2020.06.26.20140921; J Public Health [Oxf]. 2020 Aug 18;42[3]:451-60).
Dr. Rice conducted a search of Clinicaltrials.gov immediately before his presentation on Sunday, and found 41 ongoing interventional studies – “not observational studies” – looking at COVID-19 and vitamin D.
“They’re recruiting, they’re enrolling; hopefully we’ll have data soon,” he said.
Researchers have checked a lot of boxes with a resounding yes on the vitamin D question, so there’s reason to think an association does exist for ICU patients, whether or not they have COVID-19.
“Is there a theoretical benefit of vitamin D in the ICU?” Dr. Rice asked. “Yes. Is vitamin D deficient in patients in the ICU? Yes. Is that deficiency associated with poor outcomes? Yes. Can it be replaced safely? Yes.”
However, “we’re not really sure that it improves outcomes,” he said.
A chronic issue?
“Do you think it’s really an issue of the patients being critically ill with vitamin D,” or is it “a chronic issue of having low vitamin D?” asked session moderator Antine Stenbit, MD, PhD, from the University of California, San Diego.
“We don’t know for sure,” Dr. Rice said. Vitamin D might not have a lot of acute effects; it might have effects that are chronic, that work with levels over a period of time, he explained.
“It’s not clear we can correct that with a single dose or with a few days of giving a level that is adequate,” he acknowledged.
Dr. Rice is an investigator in the PETAL network. Dr. Stenbit disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
We can “stop putting money on vitamin D” to help patients who require critical care, said Todd Rice, MD, FCCP.
“Results from vitamin D trials have not been uniformly one way, but they have been pretty uniformly disappointing,” Dr. Rice, from Vanderbilt University Medical Center, Nashville, Tenn., reported at the annual meeting of the American College of Chest Physicians.
Low levels of vitamin D in critically ill COVID-19 patients have been reported in numerous recent studies, and researchers are looking for ways to boost those levels and improve outcomes.
We are seeing “the exact same story” in the critically ill COVID-19 population as we see in the general ICU population, said Dr. Rice. “The whole scenario is repeating itself. I’m pessimistic.”
Still, vitamin D levels can be elevated so, in theory, “the concept makes sense,” he said. There is evidence that, “when given enterally, the levels rise nicely” and vitamin D is absorbed reasonably well.” But is that enough?
When patients are admitted to the ICU, some biomarkers in the body are too high and others are too low. Vitamin D is often too low. So far, though, “supplementing vitamin D in the ICU has not significantly improved outcomes,” said Dr. Rice.
In the Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) trial, Dr. Rice and colleagues found no statistical benefit when a 540,000 IU boost of vitamin D was administered to 2,624 critically ill patients, as reported by Medscape Medical News.
“Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other nonfatal outcomes among critically ill, vitamin D–deficient patients,” the researchers write in their recent report.
In fact, VIOLET ended before enrollment had reached the planned 3,000-patient cohort because the statistical analysis clearly did not show benefit. Those enrolled were in the ICU because of, among other things, pneumonia, sepsis, the need for mechanical ventilation or vasopressors, and risk for acute respiratory distress syndrome.
“It doesn’t look like vitamin D is going to be the answer to our critical care problems,” Dr. Rice said in an interview.
Maintenance dose needed?
One theory suggests that VIOLET might have failed because a maintenance dose is needed after the initial boost of vitamin D.
In the ongoing VITDALIZE trial, critically ill patients with severe vitamin D deficiency (12 ng/mL or less at admission) receive an initial 540,000-IU dose followed by 4,000 IU per day.
The highly anticipated VITDALIZE results are expected in the middle of next year, Dr. Rice reported, so “let’s wait to see.”
“Vitamin D may not have an acute effect,” he theorized. “We can raise your levels, but that doesn’t give you all the benefits of having a sufficient level for a long period of time.”
Another theory suggests that a low level of vitamin D is simply a signal of the severity of disease, not a direct influence on disease pathology.
Some observational data have shown an association between low levels of vitamin D and outcomes in COVID-19 patients (Nutrients. 2020 May 9;12[5]:1359; medRxiv 2020 Apr 24. doi: 10.1101/2020.04.24.20075838; JAMA Netw Open. 2020;3[9]:e2019722; FEBS J. 2020 Jul 23;10.1111/febs.15495; Clin Endocrinol [Oxf]. 2020 Jul 3;10.1111/cen.14276), but some have shown no association (medRxiv. 2020 Jun 26. doi: 10.1101/2020.06.26.20140921; J Public Health [Oxf]. 2020 Aug 18;42[3]:451-60).
Dr. Rice conducted a search of Clinicaltrials.gov immediately before his presentation on Sunday, and found 41 ongoing interventional studies – “not observational studies” – looking at COVID-19 and vitamin D.
“They’re recruiting, they’re enrolling; hopefully we’ll have data soon,” he said.
Researchers have checked a lot of boxes with a resounding yes on the vitamin D question, so there’s reason to think an association does exist for ICU patients, whether or not they have COVID-19.
“Is there a theoretical benefit of vitamin D in the ICU?” Dr. Rice asked. “Yes. Is vitamin D deficient in patients in the ICU? Yes. Is that deficiency associated with poor outcomes? Yes. Can it be replaced safely? Yes.”
However, “we’re not really sure that it improves outcomes,” he said.
A chronic issue?
“Do you think it’s really an issue of the patients being critically ill with vitamin D,” or is it “a chronic issue of having low vitamin D?” asked session moderator Antine Stenbit, MD, PhD, from the University of California, San Diego.
“We don’t know for sure,” Dr. Rice said. Vitamin D might not have a lot of acute effects; it might have effects that are chronic, that work with levels over a period of time, he explained.
“It’s not clear we can correct that with a single dose or with a few days of giving a level that is adequate,” he acknowledged.
Dr. Rice is an investigator in the PETAL network. Dr. Stenbit disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM CHEST 2020
Include irritability in ADHD suicidality risk assessments
Irritability appears to be a potent independent predictor of increased risk for suicidality in children and adolescents with ADHD, Tomer Levy, MD, said at the virtual congress of the European College of Neuropsychopharmacology.
While there is ample evidence that ADHD is associated with increased suicidality, Dr. Levy’s recent study involving 1,516 youths aged 6-17 years attending an outpatient ADHD clinic demonstrated that this increased risk is mediated by depression and irritability in roughly equal measures. Moreover, upon controlling for those two factors in a multivariate analysis, ADHD symptoms, per se, had no direct effect on risk of suicidality as defined by suidical ideation, attempts, or self-harm.
The clinical take-home message is that assessing irritability, as well as depression, may bolster an estimate of suicidality and help in managing suicidal risk in ADHD, according to Dr. Levy, a child and adolescent psychiatrist at the Hospital for Sick Children, Toronto, and head of behavioral regulation services at the Geha Mental Health Center in Petah Tikva, Israel.
The study included separate parent- and teacher-structured reports of the youths’ ADHD symptoms, suicidality, depression, irritability, and anxiety.
In multivariate analyses, parent-reported depression accounted for 39.1% of the association between ADHD symptoms and suicidality, while irritability symptoms mediated 36.8% of the total effect. In the teachers’ reports, depression and irritability symptoms accounted for 45.3% and 38.4% of the association. Anxiety symptoms mediated 19% of the relationship between ADHD and suicidality by parental report but had no significant impact on the association according to teacher report in the recently published study.
Dr. Levy noted that, in the DSM-5, irritability cuts across diagnostic categories. It is not only a core dimension of ADHD, but of the other externalizing disorders – conduct disorder and oppositional defiant disorder – as well, and also of neurodevelopmental, internalizing, and stress-related disorders.
Interventional studies aimed at dampening irritability as a potential strategy to reduce suicidality haven’t yet been done, but they deserve research priority status, in Dr. Levy’s view. Numerous functional dimensions that influence irritability are potential targets, including aggression, negative affect, low tolerance of frustration, skewed threat perception, and impaired self-regulation, according to the psychiatrist.
Most suicidal youths are attempting to cope with mental disorders. The most prevalent of these are major depressive disorder and dysthymia, followed by externalizing disorders. And among the externalizing disorders, conduct disorder stands out in terms of the magnitude of associated suicidality risk. In a large Taiwanese national study including 3,711 adolescents with conduct disorder and 14,844 age- and sex-matched controls, conduct disorder was associated with an adjusted 5.17-fold increased risk of subsequent suicide attempts over the next 10 years in a multivariate regression analysis adjusted for other psychiatric comorbidities and demographics.
In addition to depression, irritability symptoms, and conduct problems, other risk factors that should be part of a suicidality assessment in children and adolescents with ADHD include substance use, anxiety, poor family support, and bullying and/or being bullied. But, perhaps surprisingly, not impulsivity, Dr. Levy said.
“There is a widely held perception that impulsivity imparts a risk for suicidality, and especially in the transition from ideation to attempt. However, more recent evidence fails to show a convincing association,” according to Dr. Levy.
He reported having no financial conflicts regarding his presentation.
SOURCE: Levy T. ECNP 2020, Session EDU.02.
Irritability appears to be a potent independent predictor of increased risk for suicidality in children and adolescents with ADHD, Tomer Levy, MD, said at the virtual congress of the European College of Neuropsychopharmacology.
While there is ample evidence that ADHD is associated with increased suicidality, Dr. Levy’s recent study involving 1,516 youths aged 6-17 years attending an outpatient ADHD clinic demonstrated that this increased risk is mediated by depression and irritability in roughly equal measures. Moreover, upon controlling for those two factors in a multivariate analysis, ADHD symptoms, per se, had no direct effect on risk of suicidality as defined by suidical ideation, attempts, or self-harm.
The clinical take-home message is that assessing irritability, as well as depression, may bolster an estimate of suicidality and help in managing suicidal risk in ADHD, according to Dr. Levy, a child and adolescent psychiatrist at the Hospital for Sick Children, Toronto, and head of behavioral regulation services at the Geha Mental Health Center in Petah Tikva, Israel.
The study included separate parent- and teacher-structured reports of the youths’ ADHD symptoms, suicidality, depression, irritability, and anxiety.
In multivariate analyses, parent-reported depression accounted for 39.1% of the association between ADHD symptoms and suicidality, while irritability symptoms mediated 36.8% of the total effect. In the teachers’ reports, depression and irritability symptoms accounted for 45.3% and 38.4% of the association. Anxiety symptoms mediated 19% of the relationship between ADHD and suicidality by parental report but had no significant impact on the association according to teacher report in the recently published study.
Dr. Levy noted that, in the DSM-5, irritability cuts across diagnostic categories. It is not only a core dimension of ADHD, but of the other externalizing disorders – conduct disorder and oppositional defiant disorder – as well, and also of neurodevelopmental, internalizing, and stress-related disorders.
Interventional studies aimed at dampening irritability as a potential strategy to reduce suicidality haven’t yet been done, but they deserve research priority status, in Dr. Levy’s view. Numerous functional dimensions that influence irritability are potential targets, including aggression, negative affect, low tolerance of frustration, skewed threat perception, and impaired self-regulation, according to the psychiatrist.
Most suicidal youths are attempting to cope with mental disorders. The most prevalent of these are major depressive disorder and dysthymia, followed by externalizing disorders. And among the externalizing disorders, conduct disorder stands out in terms of the magnitude of associated suicidality risk. In a large Taiwanese national study including 3,711 adolescents with conduct disorder and 14,844 age- and sex-matched controls, conduct disorder was associated with an adjusted 5.17-fold increased risk of subsequent suicide attempts over the next 10 years in a multivariate regression analysis adjusted for other psychiatric comorbidities and demographics.
In addition to depression, irritability symptoms, and conduct problems, other risk factors that should be part of a suicidality assessment in children and adolescents with ADHD include substance use, anxiety, poor family support, and bullying and/or being bullied. But, perhaps surprisingly, not impulsivity, Dr. Levy said.
“There is a widely held perception that impulsivity imparts a risk for suicidality, and especially in the transition from ideation to attempt. However, more recent evidence fails to show a convincing association,” according to Dr. Levy.
He reported having no financial conflicts regarding his presentation.
SOURCE: Levy T. ECNP 2020, Session EDU.02.
Irritability appears to be a potent independent predictor of increased risk for suicidality in children and adolescents with ADHD, Tomer Levy, MD, said at the virtual congress of the European College of Neuropsychopharmacology.
While there is ample evidence that ADHD is associated with increased suicidality, Dr. Levy’s recent study involving 1,516 youths aged 6-17 years attending an outpatient ADHD clinic demonstrated that this increased risk is mediated by depression and irritability in roughly equal measures. Moreover, upon controlling for those two factors in a multivariate analysis, ADHD symptoms, per se, had no direct effect on risk of suicidality as defined by suidical ideation, attempts, or self-harm.
The clinical take-home message is that assessing irritability, as well as depression, may bolster an estimate of suicidality and help in managing suicidal risk in ADHD, according to Dr. Levy, a child and adolescent psychiatrist at the Hospital for Sick Children, Toronto, and head of behavioral regulation services at the Geha Mental Health Center in Petah Tikva, Israel.
The study included separate parent- and teacher-structured reports of the youths’ ADHD symptoms, suicidality, depression, irritability, and anxiety.
In multivariate analyses, parent-reported depression accounted for 39.1% of the association between ADHD symptoms and suicidality, while irritability symptoms mediated 36.8% of the total effect. In the teachers’ reports, depression and irritability symptoms accounted for 45.3% and 38.4% of the association. Anxiety symptoms mediated 19% of the relationship between ADHD and suicidality by parental report but had no significant impact on the association according to teacher report in the recently published study.
Dr. Levy noted that, in the DSM-5, irritability cuts across diagnostic categories. It is not only a core dimension of ADHD, but of the other externalizing disorders – conduct disorder and oppositional defiant disorder – as well, and also of neurodevelopmental, internalizing, and stress-related disorders.
Interventional studies aimed at dampening irritability as a potential strategy to reduce suicidality haven’t yet been done, but they deserve research priority status, in Dr. Levy’s view. Numerous functional dimensions that influence irritability are potential targets, including aggression, negative affect, low tolerance of frustration, skewed threat perception, and impaired self-regulation, according to the psychiatrist.
Most suicidal youths are attempting to cope with mental disorders. The most prevalent of these are major depressive disorder and dysthymia, followed by externalizing disorders. And among the externalizing disorders, conduct disorder stands out in terms of the magnitude of associated suicidality risk. In a large Taiwanese national study including 3,711 adolescents with conduct disorder and 14,844 age- and sex-matched controls, conduct disorder was associated with an adjusted 5.17-fold increased risk of subsequent suicide attempts over the next 10 years in a multivariate regression analysis adjusted for other psychiatric comorbidities and demographics.
In addition to depression, irritability symptoms, and conduct problems, other risk factors that should be part of a suicidality assessment in children and adolescents with ADHD include substance use, anxiety, poor family support, and bullying and/or being bullied. But, perhaps surprisingly, not impulsivity, Dr. Levy said.
“There is a widely held perception that impulsivity imparts a risk for suicidality, and especially in the transition from ideation to attempt. However, more recent evidence fails to show a convincing association,” according to Dr. Levy.
He reported having no financial conflicts regarding his presentation.
SOURCE: Levy T. ECNP 2020, Session EDU.02.
FROM ECNP 2020
Key clinical point: Assessment of irritability symptoms and depression may be helpful in managing suicidality risk in ADHD.
Major finding: Parent- and teacher-reported depression and irritability symptoms mediated up to 84% of the association between pediatric ADHD and suicidality.
Study details: This cross-sectional study examined the role of irritability, depression, and anxiety in suicidality among 1,516 children and adolescents at an outpatient ADHD clinic.
Disclosures: The presenter reported having no financial conflicts regarding his study.
Source: Levy T. ECNP 2020, Session EDU.02.
COVID-19 transforms medical education: No ‘back to normal’
The COVID-19 pandemic has thrown a monkey wrench into the medical education landscape across the entire health care spectrum, disrupting the plans of medical students, residents, fellows, and program directors.
As cases of COVID-19 spread across the United States in early 2020, it became clear to training program directors that immediate action was required to meet the needs of medical learners. The challenges were unlike those surrounding the Ebola virus in 2014, “where we could more easily prevent students and trainees from exposure due to the fact that there were simply not significant numbers of cases in the United States,” Tiffany Murano, MD, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. Dr. Murano is professor of emergency medicine at Rutgers New Jersey Medical School, Newark, and president-elect of the Council of Residency Directors in Emergency Medicine. “COVID was a completely different scenario. We quickly realized that not only was personal protective equipment in short supply, but we also lacked the testing and tracking capabilities for potential exposures. Medical students and other supportive workers who were considered nonessential were removed from the clinical setting. This was after a trial of limiting who the students saw, essentially dampening the risk of exposure. But this proved to be flawed as COVID patients presented with symptoms that were unexpected.”
To complicate matters, she continued, many medical clinics either shut down, had limited access, or converted to telemedicine. Elective surgeries were canceled. This led to an overall pause in clinical medical student rotations and no direct patient care activities. As social distancing mandates were instituted, licensing examination testing centers were closed, and exams and on-campus activities were postponed.
Limiting trainee exposure
On the graduate medical education front, some training programs attempted to limit exposure of their trainees to persons under investigation for COVID-19. “As the number of COVID cases grew and encompassed most of what we were seeing in the hospital, it was obvious that residents had to play a vital part in the care of these patients,” said Dr. Murano, who is also a member of the American Council of Graduate Medical Education’s emergency review and recognition committee. “However, there was a consensus among all of the specialties that the procedures that posed the highest risk of exposure would be limited to the most senior or experienced trainees or professionals, and closely supervised by the faculty.”
ACGME activities such as accreditation site visits, clinical environment learning reviews, self-study, and resident and faculty surveys were suspended, postponed, or modified in some way, she said. The ACGME created stages of COVID status to guide sponsoring institutions to suspend learning curricula in order for patients to be cared for. Stage 1 was business as usual, “so there was no significant impact on patient care,” Dr. Murano said. “Stage 2 was increased but manageable clinical demand, while stage 3 was pandemic emergency status, where there were extraordinary circumstances where the clinical demand was so high and strenuous that the routine patient care and education really needed to be reconfigured in order to care for the patients.”
New requirements to manage training
The ACGME also implemented four requirements to manage training that were consistent among institutions, regardless of their COVID stage status. These included making sure that trainees continued to be held to work-hour limit requirements, ensuring adequate resources for training, ensuring that all residents had the appropriate level of supervision at all times, and allowing fellows to function in the core specialty in which they completed their residency training. “This was only possible if the fellows were ABMS [American Board of Medical Specialties] or AOA [American Osteopathic Association] board-eligible, or certified in their core specialty,” Dr. Murano said. “The fellows had to be appointed to the medical staff at the sponsoring institution, and their time spent on the core specialty service would be limited to 20% of their annual education time in any academic year.”
Mindful that there may have been trainees who required a 2-week quarantine period following exposure or potential exposure to COVID-19, some specialty boards showed leniency in residency time required to sit for the written exam. “Testing centers were being forced to close to observe social distancing requirements and heed sanitation recommendations, so exams were either canceled or postponed,” Dr. Murano said. “This posed a special concern for the board certification process, and those specialties with oral examinations had to make a heavy decision regarding whether or not they would allow these exams to take place. Naturally, travel among institutions was suspended or limited, or had quarantine requirements upon returning home from endemic areas. Conferences were either being canceled or converted to virtual formats.”
Subani Chandra, MD, FCCP, of the division of pulmonary, allergy, and critical care medicine at Columbia University, New York, is the internal medicine residency program director and the associate vice-chair of education for the department of medicine, and she recognized the problem created for medical trainees by the changes necessitated by the pandemic.
“The variability in caseloads and clinical exposure has given thrust to the move toward competency-based assessments rather than number- or time-based criteria for determining proficiency and graduation,” she wrote in an email interview. In addition, she noted the impact on medical meetings and the need to adapt. “Early on, before large regional and national conferences adapted to a virtual format, many were canceled altogether. Students, residents, and fellows expecting to have the opportunity to present their scholarly work were suddenly no longer able to do so. Understanding the importance of scholarly interaction, the virtual format of CHEST 2020 is designed with opportunities to present, interact with experts in the field, ask questions, network, and meet mentors.”
No return to ‘normal’
By April 2020, cases in the northeast continued to rise, particularly in the New York, New Jersey, and Connecticut region. “These states were essentially shut down in order to contain spread of the virus,” she said. “This was a real turning point because we realized that things were not going to return to ‘normal’ in the foreseeable future.” With the clinical experience essentially halted for medical students during this time, some medical schools allowed their senior students who met requirements to graduate early. “There were a lot of mixed feelings about this, recognizing that PPE [personal protective equipment] was still in short supply in many areas,” Dr. Murano said. “So, institutions took on these early graduates into roles in which they were not learners in particular, but rather medical workers. They were helping with informatics and technology, telehealth, virtual or telephone call follow-ups, and other tasks like this. There was a movement to virtual learning for the preclinical undergraduate learners, so classes were now online, recorded, or livestreamed.”
Early graduation, matching, and residencies
On April 3, the ACGME released a statement regarding graduating students early and appointing them early to the clinical learning environment. “They pointed out that institutions that were in emergency pandemic status lacked the ability to offer the comprehensive orientation and training in PPE and direct supervision required for new residents at the start of their residency,” Dr. Murano said. “Their opinion maintained that graduating medical students matriculate in their previously matched program, the National Resident Match Program start date, or other date that would be nationally determined to be the beginning of the 2020-2021 academic year.”
As May 2020 rolled around, the overriding feeling was uncertainty regarding when, if, and how medical schools were going to open in the early summer and fall. “There was also uncertainty about how graduating medical students were going to function in their new role as residents,” she said. “Same for the graduating residents. There were some who had signed contracts for jobs months before, and had them rescinded, and physicians were being furloughed due to financial hardships that institutions faced. There was also postponement of board certification exams, so people were uncertain about when they would become board certified.”
July 2020 ushered in what Dr. Murano characterized as “a whole new level of stress.” For medical students in particular, “we were entering the application season for residency positions,” she said. “Due to travel restrictions placed by various states and institutions, away rotations were limited or nonexistent. Application release dates through the Electronic Residency Application Service were moved to later in the year. The United States Medical Licensing Examination clinical skills exam was suspended, and there were modifications made for Education Commission for Foreign Medical Graduates requirements. Letters of recommendation were also going to be limited, so there had to be some degree of leniency within specialties to take a more holistic approach to review of applications for residencies.”
On the graduate medical education front, the ACGME sunsetted the initial stages and created two categories: nonemergency, which was formerly stages 1 and 2, and emergency, which was formerly stage 3. “All emergency stages are applied for and granted at 1-month intervals,” Dr. Murano said. Board certification exams were modified to accommodate either later exams or online formats, and specialties with oral examinations faced the task of potentially creating virtual oral exams.
Despite the challenges, Dr. Chandra has seen medical training programs respond with new ideas. “The flexibility and agile adaptability of the entire educational enterprise has been remarkable. The inherent uncertainty in a very dynamic and changing learning environment can be challenging. Recognizing this, many programs are creating additional ways to support the mental, emotional, physical, and financial health of students, residents, and fellows and all health care workers. The importance of this innovative response cannot be overstated.”
New learning formats
The pandemic forced Dr. Murano and other medical educators to consider unorthodox learning formats, and virtual learning took center stage. “Residency programs had shared national livestream conferences and grand rounds, and there were virtual curricula made for medical students as well as virtual simulation,” she said. “Telemedicine and telehealth really became important parts of education as well, as this may have been the only face-to-face contact that students and residents had with patients who had non–COVID-related complaints.”
To level the playing field for medical residents during this unprecedented time, a work group of the Coalition for Physician Accountability developed a set of recommendations that include limiting the number of letters of recommendation accepted, limiting the number of away rotations, and allowing alternative or less conventional letters of recommendation. “Keeping an open mind and taking a more holistic approach to applicants has really been needed during this time,” Dr. Murano said. “Virtual interview days have been agreed upon for all specialties. They’re safer, and they allow for students to virtually meet faculty and residents from distant programs that in the past would have been a deterrent due to distance and travel costs. This is not without its own downside, as it’s difficult to determine how well a student will fit into a program without [him or her] actually visiting the institution.”
Dr. Chandra agreed that virtual interviews are necessary but have inherent limitations. However, “we will all learn a lot, and very likely the future process will blend the benefits of both virtual and in-person interviews.”
‘We need to keep moving forward’
Dr. Murano concluded her presentation by noting that the COVID-19 pandemic has created opportunities for growth and innovation in medical education, “so we need to keep moving forward. I’ve heard many say that they can’t wait for things to go back to normal. But I think it’s important to go ahead to new and better ways of learning. We’re now thinking outside of the typical education model and are embracing technology and alternative means of education. We don’t know yet if this education is better, worse, or equivalent to traditional methods, but that will be determined and studied in months and years to come, so we’re certainly looking to the future.”
Dr. Murano and Dr. Chandra reported having no financial disclosures.
The COVID-19 pandemic has thrown a monkey wrench into the medical education landscape across the entire health care spectrum, disrupting the plans of medical students, residents, fellows, and program directors.
As cases of COVID-19 spread across the United States in early 2020, it became clear to training program directors that immediate action was required to meet the needs of medical learners. The challenges were unlike those surrounding the Ebola virus in 2014, “where we could more easily prevent students and trainees from exposure due to the fact that there were simply not significant numbers of cases in the United States,” Tiffany Murano, MD, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. Dr. Murano is professor of emergency medicine at Rutgers New Jersey Medical School, Newark, and president-elect of the Council of Residency Directors in Emergency Medicine. “COVID was a completely different scenario. We quickly realized that not only was personal protective equipment in short supply, but we also lacked the testing and tracking capabilities for potential exposures. Medical students and other supportive workers who were considered nonessential were removed from the clinical setting. This was after a trial of limiting who the students saw, essentially dampening the risk of exposure. But this proved to be flawed as COVID patients presented with symptoms that were unexpected.”
To complicate matters, she continued, many medical clinics either shut down, had limited access, or converted to telemedicine. Elective surgeries were canceled. This led to an overall pause in clinical medical student rotations and no direct patient care activities. As social distancing mandates were instituted, licensing examination testing centers were closed, and exams and on-campus activities were postponed.
Limiting trainee exposure
On the graduate medical education front, some training programs attempted to limit exposure of their trainees to persons under investigation for COVID-19. “As the number of COVID cases grew and encompassed most of what we were seeing in the hospital, it was obvious that residents had to play a vital part in the care of these patients,” said Dr. Murano, who is also a member of the American Council of Graduate Medical Education’s emergency review and recognition committee. “However, there was a consensus among all of the specialties that the procedures that posed the highest risk of exposure would be limited to the most senior or experienced trainees or professionals, and closely supervised by the faculty.”
ACGME activities such as accreditation site visits, clinical environment learning reviews, self-study, and resident and faculty surveys were suspended, postponed, or modified in some way, she said. The ACGME created stages of COVID status to guide sponsoring institutions to suspend learning curricula in order for patients to be cared for. Stage 1 was business as usual, “so there was no significant impact on patient care,” Dr. Murano said. “Stage 2 was increased but manageable clinical demand, while stage 3 was pandemic emergency status, where there were extraordinary circumstances where the clinical demand was so high and strenuous that the routine patient care and education really needed to be reconfigured in order to care for the patients.”
New requirements to manage training
The ACGME also implemented four requirements to manage training that were consistent among institutions, regardless of their COVID stage status. These included making sure that trainees continued to be held to work-hour limit requirements, ensuring adequate resources for training, ensuring that all residents had the appropriate level of supervision at all times, and allowing fellows to function in the core specialty in which they completed their residency training. “This was only possible if the fellows were ABMS [American Board of Medical Specialties] or AOA [American Osteopathic Association] board-eligible, or certified in their core specialty,” Dr. Murano said. “The fellows had to be appointed to the medical staff at the sponsoring institution, and their time spent on the core specialty service would be limited to 20% of their annual education time in any academic year.”
Mindful that there may have been trainees who required a 2-week quarantine period following exposure or potential exposure to COVID-19, some specialty boards showed leniency in residency time required to sit for the written exam. “Testing centers were being forced to close to observe social distancing requirements and heed sanitation recommendations, so exams were either canceled or postponed,” Dr. Murano said. “This posed a special concern for the board certification process, and those specialties with oral examinations had to make a heavy decision regarding whether or not they would allow these exams to take place. Naturally, travel among institutions was suspended or limited, or had quarantine requirements upon returning home from endemic areas. Conferences were either being canceled or converted to virtual formats.”
Subani Chandra, MD, FCCP, of the division of pulmonary, allergy, and critical care medicine at Columbia University, New York, is the internal medicine residency program director and the associate vice-chair of education for the department of medicine, and she recognized the problem created for medical trainees by the changes necessitated by the pandemic.
“The variability in caseloads and clinical exposure has given thrust to the move toward competency-based assessments rather than number- or time-based criteria for determining proficiency and graduation,” she wrote in an email interview. In addition, she noted the impact on medical meetings and the need to adapt. “Early on, before large regional and national conferences adapted to a virtual format, many were canceled altogether. Students, residents, and fellows expecting to have the opportunity to present their scholarly work were suddenly no longer able to do so. Understanding the importance of scholarly interaction, the virtual format of CHEST 2020 is designed with opportunities to present, interact with experts in the field, ask questions, network, and meet mentors.”
No return to ‘normal’
By April 2020, cases in the northeast continued to rise, particularly in the New York, New Jersey, and Connecticut region. “These states were essentially shut down in order to contain spread of the virus,” she said. “This was a real turning point because we realized that things were not going to return to ‘normal’ in the foreseeable future.” With the clinical experience essentially halted for medical students during this time, some medical schools allowed their senior students who met requirements to graduate early. “There were a lot of mixed feelings about this, recognizing that PPE [personal protective equipment] was still in short supply in many areas,” Dr. Murano said. “So, institutions took on these early graduates into roles in which they were not learners in particular, but rather medical workers. They were helping with informatics and technology, telehealth, virtual or telephone call follow-ups, and other tasks like this. There was a movement to virtual learning for the preclinical undergraduate learners, so classes were now online, recorded, or livestreamed.”
Early graduation, matching, and residencies
On April 3, the ACGME released a statement regarding graduating students early and appointing them early to the clinical learning environment. “They pointed out that institutions that were in emergency pandemic status lacked the ability to offer the comprehensive orientation and training in PPE and direct supervision required for new residents at the start of their residency,” Dr. Murano said. “Their opinion maintained that graduating medical students matriculate in their previously matched program, the National Resident Match Program start date, or other date that would be nationally determined to be the beginning of the 2020-2021 academic year.”
As May 2020 rolled around, the overriding feeling was uncertainty regarding when, if, and how medical schools were going to open in the early summer and fall. “There was also uncertainty about how graduating medical students were going to function in their new role as residents,” she said. “Same for the graduating residents. There were some who had signed contracts for jobs months before, and had them rescinded, and physicians were being furloughed due to financial hardships that institutions faced. There was also postponement of board certification exams, so people were uncertain about when they would become board certified.”
July 2020 ushered in what Dr. Murano characterized as “a whole new level of stress.” For medical students in particular, “we were entering the application season for residency positions,” she said. “Due to travel restrictions placed by various states and institutions, away rotations were limited or nonexistent. Application release dates through the Electronic Residency Application Service were moved to later in the year. The United States Medical Licensing Examination clinical skills exam was suspended, and there were modifications made for Education Commission for Foreign Medical Graduates requirements. Letters of recommendation were also going to be limited, so there had to be some degree of leniency within specialties to take a more holistic approach to review of applications for residencies.”
On the graduate medical education front, the ACGME sunsetted the initial stages and created two categories: nonemergency, which was formerly stages 1 and 2, and emergency, which was formerly stage 3. “All emergency stages are applied for and granted at 1-month intervals,” Dr. Murano said. Board certification exams were modified to accommodate either later exams or online formats, and specialties with oral examinations faced the task of potentially creating virtual oral exams.
Despite the challenges, Dr. Chandra has seen medical training programs respond with new ideas. “The flexibility and agile adaptability of the entire educational enterprise has been remarkable. The inherent uncertainty in a very dynamic and changing learning environment can be challenging. Recognizing this, many programs are creating additional ways to support the mental, emotional, physical, and financial health of students, residents, and fellows and all health care workers. The importance of this innovative response cannot be overstated.”
New learning formats
The pandemic forced Dr. Murano and other medical educators to consider unorthodox learning formats, and virtual learning took center stage. “Residency programs had shared national livestream conferences and grand rounds, and there were virtual curricula made for medical students as well as virtual simulation,” she said. “Telemedicine and telehealth really became important parts of education as well, as this may have been the only face-to-face contact that students and residents had with patients who had non–COVID-related complaints.”
To level the playing field for medical residents during this unprecedented time, a work group of the Coalition for Physician Accountability developed a set of recommendations that include limiting the number of letters of recommendation accepted, limiting the number of away rotations, and allowing alternative or less conventional letters of recommendation. “Keeping an open mind and taking a more holistic approach to applicants has really been needed during this time,” Dr. Murano said. “Virtual interview days have been agreed upon for all specialties. They’re safer, and they allow for students to virtually meet faculty and residents from distant programs that in the past would have been a deterrent due to distance and travel costs. This is not without its own downside, as it’s difficult to determine how well a student will fit into a program without [him or her] actually visiting the institution.”
Dr. Chandra agreed that virtual interviews are necessary but have inherent limitations. However, “we will all learn a lot, and very likely the future process will blend the benefits of both virtual and in-person interviews.”
‘We need to keep moving forward’
Dr. Murano concluded her presentation by noting that the COVID-19 pandemic has created opportunities for growth and innovation in medical education, “so we need to keep moving forward. I’ve heard many say that they can’t wait for things to go back to normal. But I think it’s important to go ahead to new and better ways of learning. We’re now thinking outside of the typical education model and are embracing technology and alternative means of education. We don’t know yet if this education is better, worse, or equivalent to traditional methods, but that will be determined and studied in months and years to come, so we’re certainly looking to the future.”
Dr. Murano and Dr. Chandra reported having no financial disclosures.
The COVID-19 pandemic has thrown a monkey wrench into the medical education landscape across the entire health care spectrum, disrupting the plans of medical students, residents, fellows, and program directors.
As cases of COVID-19 spread across the United States in early 2020, it became clear to training program directors that immediate action was required to meet the needs of medical learners. The challenges were unlike those surrounding the Ebola virus in 2014, “where we could more easily prevent students and trainees from exposure due to the fact that there were simply not significant numbers of cases in the United States,” Tiffany Murano, MD, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. Dr. Murano is professor of emergency medicine at Rutgers New Jersey Medical School, Newark, and president-elect of the Council of Residency Directors in Emergency Medicine. “COVID was a completely different scenario. We quickly realized that not only was personal protective equipment in short supply, but we also lacked the testing and tracking capabilities for potential exposures. Medical students and other supportive workers who were considered nonessential were removed from the clinical setting. This was after a trial of limiting who the students saw, essentially dampening the risk of exposure. But this proved to be flawed as COVID patients presented with symptoms that were unexpected.”
To complicate matters, she continued, many medical clinics either shut down, had limited access, or converted to telemedicine. Elective surgeries were canceled. This led to an overall pause in clinical medical student rotations and no direct patient care activities. As social distancing mandates were instituted, licensing examination testing centers were closed, and exams and on-campus activities were postponed.
Limiting trainee exposure
On the graduate medical education front, some training programs attempted to limit exposure of their trainees to persons under investigation for COVID-19. “As the number of COVID cases grew and encompassed most of what we were seeing in the hospital, it was obvious that residents had to play a vital part in the care of these patients,” said Dr. Murano, who is also a member of the American Council of Graduate Medical Education’s emergency review and recognition committee. “However, there was a consensus among all of the specialties that the procedures that posed the highest risk of exposure would be limited to the most senior or experienced trainees or professionals, and closely supervised by the faculty.”
ACGME activities such as accreditation site visits, clinical environment learning reviews, self-study, and resident and faculty surveys were suspended, postponed, or modified in some way, she said. The ACGME created stages of COVID status to guide sponsoring institutions to suspend learning curricula in order for patients to be cared for. Stage 1 was business as usual, “so there was no significant impact on patient care,” Dr. Murano said. “Stage 2 was increased but manageable clinical demand, while stage 3 was pandemic emergency status, where there were extraordinary circumstances where the clinical demand was so high and strenuous that the routine patient care and education really needed to be reconfigured in order to care for the patients.”
New requirements to manage training
The ACGME also implemented four requirements to manage training that were consistent among institutions, regardless of their COVID stage status. These included making sure that trainees continued to be held to work-hour limit requirements, ensuring adequate resources for training, ensuring that all residents had the appropriate level of supervision at all times, and allowing fellows to function in the core specialty in which they completed their residency training. “This was only possible if the fellows were ABMS [American Board of Medical Specialties] or AOA [American Osteopathic Association] board-eligible, or certified in their core specialty,” Dr. Murano said. “The fellows had to be appointed to the medical staff at the sponsoring institution, and their time spent on the core specialty service would be limited to 20% of their annual education time in any academic year.”
Mindful that there may have been trainees who required a 2-week quarantine period following exposure or potential exposure to COVID-19, some specialty boards showed leniency in residency time required to sit for the written exam. “Testing centers were being forced to close to observe social distancing requirements and heed sanitation recommendations, so exams were either canceled or postponed,” Dr. Murano said. “This posed a special concern for the board certification process, and those specialties with oral examinations had to make a heavy decision regarding whether or not they would allow these exams to take place. Naturally, travel among institutions was suspended or limited, or had quarantine requirements upon returning home from endemic areas. Conferences were either being canceled or converted to virtual formats.”
Subani Chandra, MD, FCCP, of the division of pulmonary, allergy, and critical care medicine at Columbia University, New York, is the internal medicine residency program director and the associate vice-chair of education for the department of medicine, and she recognized the problem created for medical trainees by the changes necessitated by the pandemic.
“The variability in caseloads and clinical exposure has given thrust to the move toward competency-based assessments rather than number- or time-based criteria for determining proficiency and graduation,” she wrote in an email interview. In addition, she noted the impact on medical meetings and the need to adapt. “Early on, before large regional and national conferences adapted to a virtual format, many were canceled altogether. Students, residents, and fellows expecting to have the opportunity to present their scholarly work were suddenly no longer able to do so. Understanding the importance of scholarly interaction, the virtual format of CHEST 2020 is designed with opportunities to present, interact with experts in the field, ask questions, network, and meet mentors.”
No return to ‘normal’
By April 2020, cases in the northeast continued to rise, particularly in the New York, New Jersey, and Connecticut region. “These states were essentially shut down in order to contain spread of the virus,” she said. “This was a real turning point because we realized that things were not going to return to ‘normal’ in the foreseeable future.” With the clinical experience essentially halted for medical students during this time, some medical schools allowed their senior students who met requirements to graduate early. “There were a lot of mixed feelings about this, recognizing that PPE [personal protective equipment] was still in short supply in many areas,” Dr. Murano said. “So, institutions took on these early graduates into roles in which they were not learners in particular, but rather medical workers. They were helping with informatics and technology, telehealth, virtual or telephone call follow-ups, and other tasks like this. There was a movement to virtual learning for the preclinical undergraduate learners, so classes were now online, recorded, or livestreamed.”
Early graduation, matching, and residencies
On April 3, the ACGME released a statement regarding graduating students early and appointing them early to the clinical learning environment. “They pointed out that institutions that were in emergency pandemic status lacked the ability to offer the comprehensive orientation and training in PPE and direct supervision required for new residents at the start of their residency,” Dr. Murano said. “Their opinion maintained that graduating medical students matriculate in their previously matched program, the National Resident Match Program start date, or other date that would be nationally determined to be the beginning of the 2020-2021 academic year.”
As May 2020 rolled around, the overriding feeling was uncertainty regarding when, if, and how medical schools were going to open in the early summer and fall. “There was also uncertainty about how graduating medical students were going to function in their new role as residents,” she said. “Same for the graduating residents. There were some who had signed contracts for jobs months before, and had them rescinded, and physicians were being furloughed due to financial hardships that institutions faced. There was also postponement of board certification exams, so people were uncertain about when they would become board certified.”
July 2020 ushered in what Dr. Murano characterized as “a whole new level of stress.” For medical students in particular, “we were entering the application season for residency positions,” she said. “Due to travel restrictions placed by various states and institutions, away rotations were limited or nonexistent. Application release dates through the Electronic Residency Application Service were moved to later in the year. The United States Medical Licensing Examination clinical skills exam was suspended, and there were modifications made for Education Commission for Foreign Medical Graduates requirements. Letters of recommendation were also going to be limited, so there had to be some degree of leniency within specialties to take a more holistic approach to review of applications for residencies.”
On the graduate medical education front, the ACGME sunsetted the initial stages and created two categories: nonemergency, which was formerly stages 1 and 2, and emergency, which was formerly stage 3. “All emergency stages are applied for and granted at 1-month intervals,” Dr. Murano said. Board certification exams were modified to accommodate either later exams or online formats, and specialties with oral examinations faced the task of potentially creating virtual oral exams.
Despite the challenges, Dr. Chandra has seen medical training programs respond with new ideas. “The flexibility and agile adaptability of the entire educational enterprise has been remarkable. The inherent uncertainty in a very dynamic and changing learning environment can be challenging. Recognizing this, many programs are creating additional ways to support the mental, emotional, physical, and financial health of students, residents, and fellows and all health care workers. The importance of this innovative response cannot be overstated.”
New learning formats
The pandemic forced Dr. Murano and other medical educators to consider unorthodox learning formats, and virtual learning took center stage. “Residency programs had shared national livestream conferences and grand rounds, and there were virtual curricula made for medical students as well as virtual simulation,” she said. “Telemedicine and telehealth really became important parts of education as well, as this may have been the only face-to-face contact that students and residents had with patients who had non–COVID-related complaints.”
To level the playing field for medical residents during this unprecedented time, a work group of the Coalition for Physician Accountability developed a set of recommendations that include limiting the number of letters of recommendation accepted, limiting the number of away rotations, and allowing alternative or less conventional letters of recommendation. “Keeping an open mind and taking a more holistic approach to applicants has really been needed during this time,” Dr. Murano said. “Virtual interview days have been agreed upon for all specialties. They’re safer, and they allow for students to virtually meet faculty and residents from distant programs that in the past would have been a deterrent due to distance and travel costs. This is not without its own downside, as it’s difficult to determine how well a student will fit into a program without [him or her] actually visiting the institution.”
Dr. Chandra agreed that virtual interviews are necessary but have inherent limitations. However, “we will all learn a lot, and very likely the future process will blend the benefits of both virtual and in-person interviews.”
‘We need to keep moving forward’
Dr. Murano concluded her presentation by noting that the COVID-19 pandemic has created opportunities for growth and innovation in medical education, “so we need to keep moving forward. I’ve heard many say that they can’t wait for things to go back to normal. But I think it’s important to go ahead to new and better ways of learning. We’re now thinking outside of the typical education model and are embracing technology and alternative means of education. We don’t know yet if this education is better, worse, or equivalent to traditional methods, but that will be determined and studied in months and years to come, so we’re certainly looking to the future.”
Dr. Murano and Dr. Chandra reported having no financial disclosures.
FROM AN SCCM VIRTUAL MEETING