Last summer, back when people traveled, I had the pleasure of being in Amsterdam for Pride Week. With a half-million tourists, it was a colorful and costumed display of LGBTQ pride, and both the streets and canals had celebrations with food, drinks, music, and displays beyond anything I could describe.

It was all not that long ago that the American Psychiatric Association classified homosexuality as a psychiatric disorder. Now we have Pride celebrations, and I don’t think twice about mentioning my brother-in-law’s husband, or a female colleague’s wife, nor am I shocked when I hear that the children of my friends are in the process of gender transition. Obviously, the idea that people express both their gender and their sexuality in diverse ways is not accepted by everyone, but we’ve come a long way toward acceptance of people who were once stigmatized and pathologized. I’ll also point out that this shift occurred despite the fact that the gay community was affected by AIDS.

There are many other differences – and illnesses – that our society has come to either accept or sympathize with more graciously over time, and yet both mental illness and substance abuse disorders remain stigmatized and punished. To put it bluntly, we have done a terrible job of making these conditions acceptable illnesses to have, even though we have done a reasonably good job of offering effective treatments. Cancer no longer carries the stigma it once did, even though cancer is a leading cause of death, and the treatments are painful, toxic, and may include the loss of body parts and hair. But if you become ill with cancer, your friends bring casseroles (or perhaps rotisserie chickens), and if you’re hospitalized with bipolar disorder or check into a drug treatment center, you’re more likely to be the recipient of judgment and even scorn.

We have to fix this. We talk about the need to destigmatize mental illness and substance use disorders, and to make these illnesses more on par with other diseases. Maybe that is the wrong call: These disorders sometimes cause people to behave in disruptive, dangerous, and illegal ways that we don’t often see with other illnesses. Frankly psychotic people may be seen as “other,” they may smell bad, they may behave in bizarre ways, and they may be frightening. Their rare acts of violence have been publicized so much that “He’s mentally ill” is accepted by the public as a full explanation for why someone would commit a mass shooting. Depression can cause people to be irritable and unpleasant, and our society equates a lack of motivation with laziness. While people may have sympathy for the suicidal thoughts and feelings of others, completed suicide leaves behind devastated survivors. People with substance use problems may become belligerent or commit crimes to support their addictions. In 2018, over 10,500 people were killed by drivers who were impaired by alcohol. I’m not sure how we destigmatize these conditions, but commercials, billboards, and educational programs aren’t doing it.
 

Fears around treatment

Perhaps our efforts need to go toward destigmatizing treatment. It is shocking to me how resistant people are to getting help, or having others know they are getting help, when treatment often renders them free from the psychological agony or misbehaviors caused by their condition.

Since I work in an outpatient setting, I see people who have made it beyond the barrier of seeking help. Almost all of my patients are willing to try medications – there is self-selection among those who chose to see a psychiatrist as opposed to another type of psychotherapist. I also believe that direct-to-consumer advertising has helped normalize the use of psychotropic medications.

When it comes to getting a higher level of care, however, the conversations are so much harder. Many of my patients insist they will never be admitted to a psychiatric unit, and when I ask depressed people if they are having suicidal thoughts, some tell me they are afraid to let me know they are for fear I might hospitalize them. This fear of hospitalization is present in people who have never been in a hospital and have only media depictions or their imaginations to go by, but I also see this with patients who have previously been hospitalized and have emerged from their inpatient stays feeling much better. While we know that any type of hospitalization involves a loss of control, unpleasant moments, and sometimes painful procedures, I have never heard anyone say that, if they were to have a second heart attack, they would refuse an admission to the cardiac care unit.

Discussions about treatment for substance use are even more difficult. People with addictions often don’t want to abstain from the substance they are using, and this is an enormous hurdle. Beyond that, they don’t like the labels that come with acknowledging a problem – words like “junkie,” “addict,” “drunk,” and “alcoholic” are hard to escape.

People fear hospitalization for many reasons: They fear losing control, they don’t recognize that they have a problem, or they rationalize their psychosis or substance use as normal. Most of all, they fear what others will think of them and what repercussions this will have for their futures. Patients would rather continue in a state of agony and dysfunction when inpatient treatment would make them better faster. This is nothing short of tragic.

What can we do? The answer is “a lot.” We need to work harder to make the hospital experience a pleasant one for patients. Inpatient units need to be clean, safe places where patients are treated with kindness, dignity, and respect and activities are appropriate, interesting, and promote healing.

Maria, a Maryland attorney, told me about her experience with inpatient treatment. “I experienced my hospitalization as jailing and acutely felt the loss of liberty, especially in the ER, where I was confined to something I recognized from my time visiting incarcerated and detained people as a holding cell, complete with a uniformed guard. I was scared to engage in any kind of meaningful self-advocacy around leaving out of fear for my license to practice law and of lengthening my time as an inpatient. As a result, I found myself concentrating on getting out, and not on getting well. With the benefit of hindsight, I can say now that my hospitalization was a lost opportunity, and the coercive elements were barriers to accessing the treatment that I needed, both at the time and in the years following the hospitalization.”

We have too many policies in place where infractions are met with force, seclusion, and sometimes restraint, and we need to be more flexible with these policies. If a psychiatric unit requires lab work prior to admission and the patient refuses, should force be used in the emergency department if there is nothing to indicate that the patient’s health is in imminent danger? And if the hospital has a policy that all psychiatric patients must disrobe to be examined for preexisting scars or contraband – this is an admission standard for some hospitals, but not others – and the patient refuses, what then? Typically, inpatients are not allowed access to their cell phones or the Internet (for many good reasons), but patients find this very upsetting; might it make sense to allow periods where they can use devices with supervision? Hospitals often forbid smoking, and people with psychiatric disorders may smoke – while it is a wonderful health ideal, is it reasonable to forbid smoking for the course of a hospitalization? Rigid adherence to policies does not always serve our patients well, and it sometimes creates dangerous situations for everyone.

We must work to get questions about psychiatric and substance use disorders removed from any job- or licensure-related forms. There is no reason to believe that people answer these forms truthfully or that including these questions protects the public in any way. What we do know is that people don’t seek help because they, like Maria, are afraid of the consequences of getting care. It doesn’t matter if a surgeon’s abilities are limited because he has episodes of hypoglycemia or past episodes of mania, and the only question on licensing forms should be about current conditions that impair the ability to work. Every district branch of the American Psychiatric Association should be actively speaking with their state professional licensing boards about the harm these questions do.

We need better treatments that have fewer side effects, and we need to acknowledge that, while getting help is the right thing to do, not everyone finds the right treatment with the first attempt and not everyone gets better. Our party line to those who feel suicidal has been “Get Help,” often with a phone number for the National Suicide Prevention Lifeline. While this is an important resource to have readily available, many of the people who die of suicide are already in active treatment. Our party line needs to change to “Get Help, and if it isn’t working, Get Different Help.” We want to be careful that our messaging does not foster a sense of hopelessness in those who have sought care and still suffer.

It’s good to talk about the potential benefits of treatment, but we don’t have enough beds and we don’t have enough mental health clinicians. There are states where psychiatric patients who have committed no crime are held in jail cells while they wait for beds to open – that we allow this is nothing short of a disgrace. The sickest patients with treatment-resistant conditions need access to the best care, and that access should not be limited by finances or networks. And while I’m here: We need our mental health professionals to spend their time working with patients, not computer screens, check boxes, and prior authorization protocols.

Finally, we need to work with the media to show positive and accurate depictions of psychiatric treatment as something that helps. We are still undoing the harm of Nurse Ratched and the depiction of electroconvulsive therapy in the 1975 film “One Flew Over the Cuckoo’s Nest,” and the current focus on mental illness and violence does nothing to help people feel comfortable seeking care.

I’ll end with one more thought from Maria: “Mental health professionals need to talk about hospitalization up front, no matter how uncomfortable, and encourage patients to think about hospitalization as a treatment option on a continuum before it is needed, so they are not approaching hospitalization as an abstract concept, often with a lot of fear and stigma attached to it, but rather as an option that they might explore in a fact-based way.”
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore. She reported having nothing to disclose.

Last summer, back when people traveled, I had the pleasure of being in Amsterdam for Pride Week. With a half-million tourists, it was a colorful and costumed display of LGBTQ pride, and both the streets and canals had celebrations with food, drinks, music, and displays beyond anything I could describe.

It was all not that long ago that the American Psychiatric Association classified homosexuality as a psychiatric disorder. Now we have Pride celebrations, and I don’t think twice about mentioning my brother-in-law’s husband, or a female colleague’s wife, nor am I shocked when I hear that the children of my friends are in the process of gender transition. Obviously, the idea that people express both their gender and their sexuality in diverse ways is not accepted by everyone, but we’ve come a long way toward acceptance of people who were once stigmatized and pathologized. I’ll also point out that this shift occurred despite the fact that the gay community was affected by AIDS.

There are many other differences – and illnesses – that our society has come to either accept or sympathize with more graciously over time, and yet both mental illness and substance abuse disorders remain stigmatized and punished. To put it bluntly, we have done a terrible job of making these conditions acceptable illnesses to have, even though we have done a reasonably good job of offering effective treatments. Cancer no longer carries the stigma it once did, even though cancer is a leading cause of death, and the treatments are painful, toxic, and may include the loss of body parts and hair. But if you become ill with cancer, your friends bring casseroles (or perhaps rotisserie chickens), and if you’re hospitalized with bipolar disorder or check into a drug treatment center, you’re more likely to be the recipient of judgment and even scorn.

We have to fix this. We talk about the need to destigmatize mental illness and substance use disorders, and to make these illnesses more on par with other diseases. Maybe that is the wrong call: These disorders sometimes cause people to behave in disruptive, dangerous, and illegal ways that we don’t often see with other illnesses. Frankly psychotic people may be seen as “other,” they may smell bad, they may behave in bizarre ways, and they may be frightening. Their rare acts of violence have been publicized so much that “He’s mentally ill” is accepted by the public as a full explanation for why someone would commit a mass shooting. Depression can cause people to be irritable and unpleasant, and our society equates a lack of motivation with laziness. While people may have sympathy for the suicidal thoughts and feelings of others, completed suicide leaves behind devastated survivors. People with substance use problems may become belligerent or commit crimes to support their addictions. In 2018, over 10,500 people were killed by drivers who were impaired by alcohol. I’m not sure how we destigmatize these conditions, but commercials, billboards, and educational programs aren’t doing it.
 

Fears around treatment

Perhaps our efforts need to go toward destigmatizing treatment. It is shocking to me how resistant people are to getting help, or having others know they are getting help, when treatment often renders them free from the psychological agony or misbehaviors caused by their condition.

Since I work in an outpatient setting, I see people who have made it beyond the barrier of seeking help. Almost all of my patients are willing to try medications – there is self-selection among those who chose to see a psychiatrist as opposed to another type of psychotherapist. I also believe that direct-to-consumer advertising has helped normalize the use of psychotropic medications.

When it comes to getting a higher level of care, however, the conversations are so much harder. Many of my patients insist they will never be admitted to a psychiatric unit, and when I ask depressed people if they are having suicidal thoughts, some tell me they are afraid to let me know they are for fear I might hospitalize them. This fear of hospitalization is present in people who have never been in a hospital and have only media depictions or their imaginations to go by, but I also see this with patients who have previously been hospitalized and have emerged from their inpatient stays feeling much better. While we know that any type of hospitalization involves a loss of control, unpleasant moments, and sometimes painful procedures, I have never heard anyone say that, if they were to have a second heart attack, they would refuse an admission to the cardiac care unit.

Discussions about treatment for substance use are even more difficult. People with addictions often don’t want to abstain from the substance they are using, and this is an enormous hurdle. Beyond that, they don’t like the labels that come with acknowledging a problem – words like “junkie,” “addict,” “drunk,” and “alcoholic” are hard to escape.

People fear hospitalization for many reasons: They fear losing control, they don’t recognize that they have a problem, or they rationalize their psychosis or substance use as normal. Most of all, they fear what others will think of them and what repercussions this will have for their futures. Patients would rather continue in a state of agony and dysfunction when inpatient treatment would make them better faster. This is nothing short of tragic.

What can we do? The answer is “a lot.” We need to work harder to make the hospital experience a pleasant one for patients. Inpatient units need to be clean, safe places where patients are treated with kindness, dignity, and respect and activities are appropriate, interesting, and promote healing.

Maria, a Maryland attorney, told me about her experience with inpatient treatment. “I experienced my hospitalization as jailing and acutely felt the loss of liberty, especially in the ER, where I was confined to something I recognized from my time visiting incarcerated and detained people as a holding cell, complete with a uniformed guard. I was scared to engage in any kind of meaningful self-advocacy around leaving out of fear for my license to practice law and of lengthening my time as an inpatient. As a result, I found myself concentrating on getting out, and not on getting well. With the benefit of hindsight, I can say now that my hospitalization was a lost opportunity, and the coercive elements were barriers to accessing the treatment that I needed, both at the time and in the years following the hospitalization.”

We have too many policies in place where infractions are met with force, seclusion, and sometimes restraint, and we need to be more flexible with these policies. If a psychiatric unit requires lab work prior to admission and the patient refuses, should force be used in the emergency department if there is nothing to indicate that the patient’s health is in imminent danger? And if the hospital has a policy that all psychiatric patients must disrobe to be examined for preexisting scars or contraband – this is an admission standard for some hospitals, but not others – and the patient refuses, what then? Typically, inpatients are not allowed access to their cell phones or the Internet (for many good reasons), but patients find this very upsetting; might it make sense to allow periods where they can use devices with supervision? Hospitals often forbid smoking, and people with psychiatric disorders may smoke – while it is a wonderful health ideal, is it reasonable to forbid smoking for the course of a hospitalization? Rigid adherence to policies does not always serve our patients well, and it sometimes creates dangerous situations for everyone.

We must work to get questions about psychiatric and substance use disorders removed from any job- or licensure-related forms. There is no reason to believe that people answer these forms truthfully or that including these questions protects the public in any way. What we do know is that people don’t seek help because they, like Maria, are afraid of the consequences of getting care. It doesn’t matter if a surgeon’s abilities are limited because he has episodes of hypoglycemia or past episodes of mania, and the only question on licensing forms should be about current conditions that impair the ability to work. Every district branch of the American Psychiatric Association should be actively speaking with their state professional licensing boards about the harm these questions do.

We need better treatments that have fewer side effects, and we need to acknowledge that, while getting help is the right thing to do, not everyone finds the right treatment with the first attempt and not everyone gets better. Our party line to those who feel suicidal has been “Get Help,” often with a phone number for the National Suicide Prevention Lifeline. While this is an important resource to have readily available, many of the people who die of suicide are already in active treatment. Our party line needs to change to “Get Help, and if it isn’t working, Get Different Help.” We want to be careful that our messaging does not foster a sense of hopelessness in those who have sought care and still suffer.

It’s good to talk about the potential benefits of treatment, but we don’t have enough beds and we don’t have enough mental health clinicians. There are states where psychiatric patients who have committed no crime are held in jail cells while they wait for beds to open – that we allow this is nothing short of a disgrace. The sickest patients with treatment-resistant conditions need access to the best care, and that access should not be limited by finances or networks. And while I’m here: We need our mental health professionals to spend their time working with patients, not computer screens, check boxes, and prior authorization protocols.

Finally, we need to work with the media to show positive and accurate depictions of psychiatric treatment as something that helps. We are still undoing the harm of Nurse Ratched and the depiction of electroconvulsive therapy in the 1975 film “One Flew Over the Cuckoo’s Nest,” and the current focus on mental illness and violence does nothing to help people feel comfortable seeking care.

I’ll end with one more thought from Maria: “Mental health professionals need to talk about hospitalization up front, no matter how uncomfortable, and encourage patients to think about hospitalization as a treatment option on a continuum before it is needed, so they are not approaching hospitalization as an abstract concept, often with a lot of fear and stigma attached to it, but rather as an option that they might explore in a fact-based way.”
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore. She reported having nothing to disclose.

Last summer, back when people traveled, I had the pleasure of being in Amsterdam for Pride Week. With a half-million tourists, it was a colorful and costumed display of LGBTQ pride, and both the streets and canals had celebrations with food, drinks, music, and displays beyond anything I could describe.

It was all not that long ago that the American Psychiatric Association classified homosexuality as a psychiatric disorder. Now we have Pride celebrations, and I don’t think twice about mentioning my brother-in-law’s husband, or a female colleague’s wife, nor am I shocked when I hear that the children of my friends are in the process of gender transition. Obviously, the idea that people express both their gender and their sexuality in diverse ways is not accepted by everyone, but we’ve come a long way toward acceptance of people who were once stigmatized and pathologized. I’ll also point out that this shift occurred despite the fact that the gay community was affected by AIDS.

There are many other differences – and illnesses – that our society has come to either accept or sympathize with more graciously over time, and yet both mental illness and substance abuse disorders remain stigmatized and punished. To put it bluntly, we have done a terrible job of making these conditions acceptable illnesses to have, even though we have done a reasonably good job of offering effective treatments. Cancer no longer carries the stigma it once did, even though cancer is a leading cause of death, and the treatments are painful, toxic, and may include the loss of body parts and hair. But if you become ill with cancer, your friends bring casseroles (or perhaps rotisserie chickens), and if you’re hospitalized with bipolar disorder or check into a drug treatment center, you’re more likely to be the recipient of judgment and even scorn.

We have to fix this. We talk about the need to destigmatize mental illness and substance use disorders, and to make these illnesses more on par with other diseases. Maybe that is the wrong call: These disorders sometimes cause people to behave in disruptive, dangerous, and illegal ways that we don’t often see with other illnesses. Frankly psychotic people may be seen as “other,” they may smell bad, they may behave in bizarre ways, and they may be frightening. Their rare acts of violence have been publicized so much that “He’s mentally ill” is accepted by the public as a full explanation for why someone would commit a mass shooting. Depression can cause people to be irritable and unpleasant, and our society equates a lack of motivation with laziness. While people may have sympathy for the suicidal thoughts and feelings of others, completed suicide leaves behind devastated survivors. People with substance use problems may become belligerent or commit crimes to support their addictions. In 2018, over 10,500 people were killed by drivers who were impaired by alcohol. I’m not sure how we destigmatize these conditions, but commercials, billboards, and educational programs aren’t doing it.
 

Fears around treatment

Perhaps our efforts need to go toward destigmatizing treatment. It is shocking to me how resistant people are to getting help, or having others know they are getting help, when treatment often renders them free from the psychological agony or misbehaviors caused by their condition.

Since I work in an outpatient setting, I see people who have made it beyond the barrier of seeking help. Almost all of my patients are willing to try medications – there is self-selection among those who chose to see a psychiatrist as opposed to another type of psychotherapist. I also believe that direct-to-consumer advertising has helped normalize the use of psychotropic medications.

When it comes to getting a higher level of care, however, the conversations are so much harder. Many of my patients insist they will never be admitted to a psychiatric unit, and when I ask depressed people if they are having suicidal thoughts, some tell me they are afraid to let me know they are for fear I might hospitalize them. This fear of hospitalization is present in people who have never been in a hospital and have only media depictions or their imaginations to go by, but I also see this with patients who have previously been hospitalized and have emerged from their inpatient stays feeling much better. While we know that any type of hospitalization involves a loss of control, unpleasant moments, and sometimes painful procedures, I have never heard anyone say that, if they were to have a second heart attack, they would refuse an admission to the cardiac care unit.

Discussions about treatment for substance use are even more difficult. People with addictions often don’t want to abstain from the substance they are using, and this is an enormous hurdle. Beyond that, they don’t like the labels that come with acknowledging a problem – words like “junkie,” “addict,” “drunk,” and “alcoholic” are hard to escape.

People fear hospitalization for many reasons: They fear losing control, they don’t recognize that they have a problem, or they rationalize their psychosis or substance use as normal. Most of all, they fear what others will think of them and what repercussions this will have for their futures. Patients would rather continue in a state of agony and dysfunction when inpatient treatment would make them better faster. This is nothing short of tragic.

What can we do? The answer is “a lot.” We need to work harder to make the hospital experience a pleasant one for patients. Inpatient units need to be clean, safe places where patients are treated with kindness, dignity, and respect and activities are appropriate, interesting, and promote healing.

Maria, a Maryland attorney, told me about her experience with inpatient treatment. “I experienced my hospitalization as jailing and acutely felt the loss of liberty, especially in the ER, where I was confined to something I recognized from my time visiting incarcerated and detained people as a holding cell, complete with a uniformed guard. I was scared to engage in any kind of meaningful self-advocacy around leaving out of fear for my license to practice law and of lengthening my time as an inpatient. As a result, I found myself concentrating on getting out, and not on getting well. With the benefit of hindsight, I can say now that my hospitalization was a lost opportunity, and the coercive elements were barriers to accessing the treatment that I needed, both at the time and in the years following the hospitalization.”

We have too many policies in place where infractions are met with force, seclusion, and sometimes restraint, and we need to be more flexible with these policies. If a psychiatric unit requires lab work prior to admission and the patient refuses, should force be used in the emergency department if there is nothing to indicate that the patient’s health is in imminent danger? And if the hospital has a policy that all psychiatric patients must disrobe to be examined for preexisting scars or contraband – this is an admission standard for some hospitals, but not others – and the patient refuses, what then? Typically, inpatients are not allowed access to their cell phones or the Internet (for many good reasons), but patients find this very upsetting; might it make sense to allow periods where they can use devices with supervision? Hospitals often forbid smoking, and people with psychiatric disorders may smoke – while it is a wonderful health ideal, is it reasonable to forbid smoking for the course of a hospitalization? Rigid adherence to policies does not always serve our patients well, and it sometimes creates dangerous situations for everyone.

We must work to get questions about psychiatric and substance use disorders removed from any job- or licensure-related forms. There is no reason to believe that people answer these forms truthfully or that including these questions protects the public in any way. What we do know is that people don’t seek help because they, like Maria, are afraid of the consequences of getting care. It doesn’t matter if a surgeon’s abilities are limited because he has episodes of hypoglycemia or past episodes of mania, and the only question on licensing forms should be about current conditions that impair the ability to work. Every district branch of the American Psychiatric Association should be actively speaking with their state professional licensing boards about the harm these questions do.

We need better treatments that have fewer side effects, and we need to acknowledge that, while getting help is the right thing to do, not everyone finds the right treatment with the first attempt and not everyone gets better. Our party line to those who feel suicidal has been “Get Help,” often with a phone number for the National Suicide Prevention Lifeline. While this is an important resource to have readily available, many of the people who die of suicide are already in active treatment. Our party line needs to change to “Get Help, and if it isn’t working, Get Different Help.” We want to be careful that our messaging does not foster a sense of hopelessness in those who have sought care and still suffer.

It’s good to talk about the potential benefits of treatment, but we don’t have enough beds and we don’t have enough mental health clinicians. There are states where psychiatric patients who have committed no crime are held in jail cells while they wait for beds to open – that we allow this is nothing short of a disgrace. The sickest patients with treatment-resistant conditions need access to the best care, and that access should not be limited by finances or networks. And while I’m here: We need our mental health professionals to spend their time working with patients, not computer screens, check boxes, and prior authorization protocols.

Finally, we need to work with the media to show positive and accurate depictions of psychiatric treatment as something that helps. We are still undoing the harm of Nurse Ratched and the depiction of electroconvulsive therapy in the 1975 film “One Flew Over the Cuckoo’s Nest,” and the current focus on mental illness and violence does nothing to help people feel comfortable seeking care.

I’ll end with one more thought from Maria: “Mental health professionals need to talk about hospitalization up front, no matter how uncomfortable, and encourage patients to think about hospitalization as a treatment option on a continuum before it is needed, so they are not approaching hospitalization as an abstract concept, often with a lot of fear and stigma attached to it, but rather as an option that they might explore in a fact-based way.”
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore. She reported having nothing to disclose.

A recent Medscape survey found there were high levels of loneliness, stress, and burnout in physicians during the COVID-19 pandemic. Isolation and relationship stress add to the problem.

Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.

As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.

Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.

“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”

Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
 

Physicians feel a sense of betrayal

Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.

“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.

Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.

Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.

The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
 

Not what they signed up for

Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)

Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.

“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.

The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.

David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.

“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.

Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
 

New situations create more anxiety

Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.

Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
 

Relationships became more challenging

Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.

One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”

Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”

On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”

As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.

Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.

Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”

Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.

“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
 

Socializing outside the box

Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.

Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.

“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”

Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.

Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
 

The importance of ‘fixing’ the workplace

Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.

At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.

Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.

Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.

Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”

Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”

For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.

This article first appeared on Medscape.com.

A recent Medscape survey found there were high levels of loneliness, stress, and burnout in physicians during the COVID-19 pandemic. Isolation and relationship stress add to the problem.

Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.

As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.

Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.

“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”

Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
 

Physicians feel a sense of betrayal

Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.

“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.

Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.

Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.

The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
 

Not what they signed up for

Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)

Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.

“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.

The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.

David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.

“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.

Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
 

New situations create more anxiety

Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.

Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
 

Relationships became more challenging

Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.

One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”

Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”

On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”

As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.

Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.

Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”

Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.

“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
 

Socializing outside the box

Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.

Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.

“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”

Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.

Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
 

The importance of ‘fixing’ the workplace

Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.

At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.

Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.

Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.

Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”

Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”

For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.

This article first appeared on Medscape.com.

A recent Medscape survey found there were high levels of loneliness, stress, and burnout in physicians during the COVID-19 pandemic. Isolation and relationship stress add to the problem.

Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.

As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.

Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.

“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”

Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
 

Physicians feel a sense of betrayal

Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.

“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.

Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.

Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.

The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
 

Not what they signed up for

Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)

Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.

“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.

The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.

David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.

“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.

Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
 

New situations create more anxiety

Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.

Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
 

Relationships became more challenging

Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.

One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”

Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”

On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”

As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.

Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.

Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”

Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.

“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
 

Socializing outside the box

Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.

Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.

“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”

Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.

Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
 

The importance of ‘fixing’ the workplace

Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.

At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.

Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.

Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.

Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”

Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”

For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.

This article first appeared on Medscape.com.

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

General anesthesia for ECT gets short shrift in the psychiatric literature, yet it’s an indispensable part of the procedure, with a major impact on its safety and outcomes, Alexander Sartorius, MD, asserted at the virtual congress of the European College of Neuropsychopharmacology.

Just how neglected is the topic?

“The two bibles of ECT – the American Psychiatric Association’s ‘The Practice of Electroconvulsive Therapy’ and Richard Abrams’s ‘Electroconvulsive Therapy,’ contain only three pages on anesthesia out of several hundred pages,” noted Dr. Sartorius, a psychiatrist at the Central Institute of Mental Health in Mannheim, Germany.

Dr. Sartorius, who has published extensively on the management of general anesthesia in ECT, offered fresh insights into its optimization. He also shared how to swiftly identify and deal with its main side effects.

General anesthesia is an essential part of ECT for only one reason: Not to spare the patient from pain or trauma, as is widely supposed, but simply to avoid awareness of the muscle relaxant that’s given to prevent bone fractures and other injuries caused by motor seizure, the psychiatrist explained.

Four anesthetic agents traditionally used for ECT have fallen by the wayside. The two barbiturates, thiopental and methohexital, have problematic anticonvulsant properties that complicate their use in a procedure whose whole purpose is to induce a seizure. Plus, they have black-box warnings in some countries. Etomidate, in contrast, has no anticonvulsant effect; however, anesthesiologists are increasingly leery of the drug. A single dose completely suppresses the hypothalamic-pituitary-adrenal axis for more than 24 hours, and mounting evidence suggests that etomidate may be associated with increased mortality.

Dr. Sartorius is a fan of ketofol, a combination of two anesthetic agents – ketamine and propofol – that provide rapid onset and cessation of action, pharmacokinetic predictability, synergistic efficacy, and minimal adverse effects when the two drugs are given in doses lower than standard as monotherapy.

Propofol has attractive qualities as an anesthetic, but it is a very potent anticonvulsant with an adverse effect on seizure quality and duration. When used alone for general anesthesia in ECT, a higher stimulation dose is often necessary to achieve adequate seizure quality, which in turn may produce worse cognitive side effects. In contrast, ketamine, which is listed as an essential drug by the World Health Organization, has no anticonvulsive effects.

“My conclusion about ketamine alone is it has less side effects than feared, and it’s probably not more but definitely not less effective than the grand old four anesthetic agents,” Dr. Sartorius said.

Plus, ketamine shows promise as an antidepressant agent in and of itself. Moreover, the fact that patients require a lower ECT stimulation dose while under the influence of ketamine could result in fewer cognitive side effects, although that’s conjecture at this point, he added.

Ketofol is often administered in a 1:1 ratio of propofol to ketamine. That’s not optimum for each individual patient undergoing ECT, as in many cases it results in so much propofol that seizure quality is diminished, in Dr. Sartorius’s experience. He, therefore, recently published a retrospective study of 52 patients who received 919 ECT sessions with empirically determined doses of S-ketamine plus propofol for anesthesia. The endpoints were time in the recovery room and seizure duration and quality. Seizure quality was assessed as a composite of the ratio of duration of motor response to EEG seizure duration, peak heart rate, midictal amplitude, maximal interhemispheric coherence, and postictal suppression index.

The optimal S-ketamine/propofol ratio in terms of seizure quality was 1.52:1, with a mean relative dose of 0.72 mg/kg of S-ketamine and 0.54 mg/kg of propofol.

His team uses only the S-enantiomer of ketamine, not the racemic mixture known as ketamine, but his study results would translate to a 3:1 ratio of racemic ketamine to propofol, Dr. Sartorius said.

Time in the recovery room was dependent upon return of cardiorespiratory function and orientation status to baseline pre-ECT levels. Longer recovery room time proved to be significantly related to older age. The S-ketamine dose wasn’t a significant factor.

Propofol was injected prior to S-ketamine in all patients. This was followed 1-2 minutes later by administration of succinylcholine as a muscle relaxant. It’s important to then wait for at least another 2-3 minutes before delivering the ECT stimulation. Dr. Sartorius and others have demonstrated that waiting at least 4 minutes between anesthesia induction and delivery of the ECT charge results in a better-quality seizure.

“We have a timer running so we can be sure to wait longer than 4 minutes. That’s a large advantage if you want to reduce the anticonvulsant property of propofol,” he explained.
 

Anesthesia-related side effects

Dr. Sartorius addressed postictal agitation syndrome, postanesthetic shivering, cardiac arrhythmias, and hypersalivation.

Postictal agitation syndrome: The deeper the level of sedation, the less likely this complication. Historically, in ECT without anesthesia, the incidence of postictal agitation was as high as 50%. At the center where Dr. Sartorius works, it’s 2%-3%. The use of intraprocedural bispectral index monitoring of the achieved deepest level of sedation allows highly accurate prediction of postictal agitation.

“Do not restrain,” he advised. “Patients are aware of this problematic situation. You have to keep everything calm and use the least possible amount of physical limitation. The good thing is that it’s self-limited within 20 minutes in most cases. But in severe cases you have to escalate staff immediately, and you may want to use 10 mg of IV diazepam. The most important message is you have to increase the dose of your anesthetic with the next ECT; a lower dose of anesthetic is not the solution.”

It is also important to watch for these possible complications:

• Postanesthetic shivering: This is a rare but potentially fatal complication. It’s important to be familiar with the grading system, and to recognize that grade 3 or 4 post-anesthetic shivering requires treatment. “The treatment of choice is clonidine. That should always be with you when you do ECT,” Dr. Sartorius observed.
• Cardiac arrhythmias: “ECT is a proarrhythmic intervention; don’t forget that,” he said.
• Poststimulation asystole: This occurs in more than half of treated patients. It’s caused by the current, not the seizure, and it stops within a few seconds after the current halts. If the asystoles bother the patient, try switching to bifrontal electrode placement. Right unilateral stimulation has been shown to increase the likelihood of asystole by 207-fold, compared with bifrontal stimulation.
• Tachycardia: This is another common complication of ECT. It responds well to a short-acting beta-blocker.
• Hypersalivation: The treatment of choice is glycopyrrolate, a muscarinic receptor antagonist that doesn’t cross the blood-brain barrier.

Dr. Sartorius reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Sartorius A et al. ECNP 2020, Session EDU03.02.

General anesthesia for ECT gets short shrift in the psychiatric literature, yet it’s an indispensable part of the procedure, with a major impact on its safety and outcomes, Alexander Sartorius, MD, asserted at the virtual congress of the European College of Neuropsychopharmacology.

Just how neglected is the topic?

“The two bibles of ECT – the American Psychiatric Association’s ‘The Practice of Electroconvulsive Therapy’ and Richard Abrams’s ‘Electroconvulsive Therapy,’ contain only three pages on anesthesia out of several hundred pages,” noted Dr. Sartorius, a psychiatrist at the Central Institute of Mental Health in Mannheim, Germany.

Dr. Sartorius, who has published extensively on the management of general anesthesia in ECT, offered fresh insights into its optimization. He also shared how to swiftly identify and deal with its main side effects.

General anesthesia is an essential part of ECT for only one reason: Not to spare the patient from pain or trauma, as is widely supposed, but simply to avoid awareness of the muscle relaxant that’s given to prevent bone fractures and other injuries caused by motor seizure, the psychiatrist explained.

Four anesthetic agents traditionally used for ECT have fallen by the wayside. The two barbiturates, thiopental and methohexital, have problematic anticonvulsant properties that complicate their use in a procedure whose whole purpose is to induce a seizure. Plus, they have black-box warnings in some countries. Etomidate, in contrast, has no anticonvulsant effect; however, anesthesiologists are increasingly leery of the drug. A single dose completely suppresses the hypothalamic-pituitary-adrenal axis for more than 24 hours, and mounting evidence suggests that etomidate may be associated with increased mortality.

Dr. Sartorius is a fan of ketofol, a combination of two anesthetic agents – ketamine and propofol – that provide rapid onset and cessation of action, pharmacokinetic predictability, synergistic efficacy, and minimal adverse effects when the two drugs are given in doses lower than standard as monotherapy.

Propofol has attractive qualities as an anesthetic, but it is a very potent anticonvulsant with an adverse effect on seizure quality and duration. When used alone for general anesthesia in ECT, a higher stimulation dose is often necessary to achieve adequate seizure quality, which in turn may produce worse cognitive side effects. In contrast, ketamine, which is listed as an essential drug by the World Health Organization, has no anticonvulsive effects.

“My conclusion about ketamine alone is it has less side effects than feared, and it’s probably not more but definitely not less effective than the grand old four anesthetic agents,” Dr. Sartorius said.

Plus, ketamine shows promise as an antidepressant agent in and of itself. Moreover, the fact that patients require a lower ECT stimulation dose while under the influence of ketamine could result in fewer cognitive side effects, although that’s conjecture at this point, he added.

Ketofol is often administered in a 1:1 ratio of propofol to ketamine. That’s not optimum for each individual patient undergoing ECT, as in many cases it results in so much propofol that seizure quality is diminished, in Dr. Sartorius’s experience. He, therefore, recently published a retrospective study of 52 patients who received 919 ECT sessions with empirically determined doses of S-ketamine plus propofol for anesthesia. The endpoints were time in the recovery room and seizure duration and quality. Seizure quality was assessed as a composite of the ratio of duration of motor response to EEG seizure duration, peak heart rate, midictal amplitude, maximal interhemispheric coherence, and postictal suppression index.

The optimal S-ketamine/propofol ratio in terms of seizure quality was 1.52:1, with a mean relative dose of 0.72 mg/kg of S-ketamine and 0.54 mg/kg of propofol.

His team uses only the S-enantiomer of ketamine, not the racemic mixture known as ketamine, but his study results would translate to a 3:1 ratio of racemic ketamine to propofol, Dr. Sartorius said.

Time in the recovery room was dependent upon return of cardiorespiratory function and orientation status to baseline pre-ECT levels. Longer recovery room time proved to be significantly related to older age. The S-ketamine dose wasn’t a significant factor.

Propofol was injected prior to S-ketamine in all patients. This was followed 1-2 minutes later by administration of succinylcholine as a muscle relaxant. It’s important to then wait for at least another 2-3 minutes before delivering the ECT stimulation. Dr. Sartorius and others have demonstrated that waiting at least 4 minutes between anesthesia induction and delivery of the ECT charge results in a better-quality seizure.

“We have a timer running so we can be sure to wait longer than 4 minutes. That’s a large advantage if you want to reduce the anticonvulsant property of propofol,” he explained.
 

Anesthesia-related side effects

Dr. Sartorius addressed postictal agitation syndrome, postanesthetic shivering, cardiac arrhythmias, and hypersalivation.

Postictal agitation syndrome: The deeper the level of sedation, the less likely this complication. Historically, in ECT without anesthesia, the incidence of postictal agitation was as high as 50%. At the center where Dr. Sartorius works, it’s 2%-3%. The use of intraprocedural bispectral index monitoring of the achieved deepest level of sedation allows highly accurate prediction of postictal agitation.

“Do not restrain,” he advised. “Patients are aware of this problematic situation. You have to keep everything calm and use the least possible amount of physical limitation. The good thing is that it’s self-limited within 20 minutes in most cases. But in severe cases you have to escalate staff immediately, and you may want to use 10 mg of IV diazepam. The most important message is you have to increase the dose of your anesthetic with the next ECT; a lower dose of anesthetic is not the solution.”

It is also important to watch for these possible complications:

• Postanesthetic shivering: This is a rare but potentially fatal complication. It’s important to be familiar with the grading system, and to recognize that grade 3 or 4 post-anesthetic shivering requires treatment. “The treatment of choice is clonidine. That should always be with you when you do ECT,” Dr. Sartorius observed.
• Cardiac arrhythmias: “ECT is a proarrhythmic intervention; don’t forget that,” he said.
• Poststimulation asystole: This occurs in more than half of treated patients. It’s caused by the current, not the seizure, and it stops within a few seconds after the current halts. If the asystoles bother the patient, try switching to bifrontal electrode placement. Right unilateral stimulation has been shown to increase the likelihood of asystole by 207-fold, compared with bifrontal stimulation.
• Tachycardia: This is another common complication of ECT. It responds well to a short-acting beta-blocker.
• Hypersalivation: The treatment of choice is glycopyrrolate, a muscarinic receptor antagonist that doesn’t cross the blood-brain barrier.

Dr. Sartorius reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Sartorius A et al. ECNP 2020, Session EDU03.02.

General anesthesia for ECT gets short shrift in the psychiatric literature, yet it’s an indispensable part of the procedure, with a major impact on its safety and outcomes, Alexander Sartorius, MD, asserted at the virtual congress of the European College of Neuropsychopharmacology.

Just how neglected is the topic?

“The two bibles of ECT – the American Psychiatric Association’s ‘The Practice of Electroconvulsive Therapy’ and Richard Abrams’s ‘Electroconvulsive Therapy,’ contain only three pages on anesthesia out of several hundred pages,” noted Dr. Sartorius, a psychiatrist at the Central Institute of Mental Health in Mannheim, Germany.

Dr. Sartorius, who has published extensively on the management of general anesthesia in ECT, offered fresh insights into its optimization. He also shared how to swiftly identify and deal with its main side effects.

General anesthesia is an essential part of ECT for only one reason: Not to spare the patient from pain or trauma, as is widely supposed, but simply to avoid awareness of the muscle relaxant that’s given to prevent bone fractures and other injuries caused by motor seizure, the psychiatrist explained.

Four anesthetic agents traditionally used for ECT have fallen by the wayside. The two barbiturates, thiopental and methohexital, have problematic anticonvulsant properties that complicate their use in a procedure whose whole purpose is to induce a seizure. Plus, they have black-box warnings in some countries. Etomidate, in contrast, has no anticonvulsant effect; however, anesthesiologists are increasingly leery of the drug. A single dose completely suppresses the hypothalamic-pituitary-adrenal axis for more than 24 hours, and mounting evidence suggests that etomidate may be associated with increased mortality.

Dr. Sartorius is a fan of ketofol, a combination of two anesthetic agents – ketamine and propofol – that provide rapid onset and cessation of action, pharmacokinetic predictability, synergistic efficacy, and minimal adverse effects when the two drugs are given in doses lower than standard as monotherapy.

Propofol has attractive qualities as an anesthetic, but it is a very potent anticonvulsant with an adverse effect on seizure quality and duration. When used alone for general anesthesia in ECT, a higher stimulation dose is often necessary to achieve adequate seizure quality, which in turn may produce worse cognitive side effects. In contrast, ketamine, which is listed as an essential drug by the World Health Organization, has no anticonvulsive effects.

“My conclusion about ketamine alone is it has less side effects than feared, and it’s probably not more but definitely not less effective than the grand old four anesthetic agents,” Dr. Sartorius said.

Plus, ketamine shows promise as an antidepressant agent in and of itself. Moreover, the fact that patients require a lower ECT stimulation dose while under the influence of ketamine could result in fewer cognitive side effects, although that’s conjecture at this point, he added.

Ketofol is often administered in a 1:1 ratio of propofol to ketamine. That’s not optimum for each individual patient undergoing ECT, as in many cases it results in so much propofol that seizure quality is diminished, in Dr. Sartorius’s experience. He, therefore, recently published a retrospective study of 52 patients who received 919 ECT sessions with empirically determined doses of S-ketamine plus propofol for anesthesia. The endpoints were time in the recovery room and seizure duration and quality. Seizure quality was assessed as a composite of the ratio of duration of motor response to EEG seizure duration, peak heart rate, midictal amplitude, maximal interhemispheric coherence, and postictal suppression index.

The optimal S-ketamine/propofol ratio in terms of seizure quality was 1.52:1, with a mean relative dose of 0.72 mg/kg of S-ketamine and 0.54 mg/kg of propofol.

His team uses only the S-enantiomer of ketamine, not the racemic mixture known as ketamine, but his study results would translate to a 3:1 ratio of racemic ketamine to propofol, Dr. Sartorius said.

Time in the recovery room was dependent upon return of cardiorespiratory function and orientation status to baseline pre-ECT levels. Longer recovery room time proved to be significantly related to older age. The S-ketamine dose wasn’t a significant factor.

Propofol was injected prior to S-ketamine in all patients. This was followed 1-2 minutes later by administration of succinylcholine as a muscle relaxant. It’s important to then wait for at least another 2-3 minutes before delivering the ECT stimulation. Dr. Sartorius and others have demonstrated that waiting at least 4 minutes between anesthesia induction and delivery of the ECT charge results in a better-quality seizure.

“We have a timer running so we can be sure to wait longer than 4 minutes. That’s a large advantage if you want to reduce the anticonvulsant property of propofol,” he explained.
 

Anesthesia-related side effects

Dr. Sartorius addressed postictal agitation syndrome, postanesthetic shivering, cardiac arrhythmias, and hypersalivation.

Postictal agitation syndrome: The deeper the level of sedation, the less likely this complication. Historically, in ECT without anesthesia, the incidence of postictal agitation was as high as 50%. At the center where Dr. Sartorius works, it’s 2%-3%. The use of intraprocedural bispectral index monitoring of the achieved deepest level of sedation allows highly accurate prediction of postictal agitation.

“Do not restrain,” he advised. “Patients are aware of this problematic situation. You have to keep everything calm and use the least possible amount of physical limitation. The good thing is that it’s self-limited within 20 minutes in most cases. But in severe cases you have to escalate staff immediately, and you may want to use 10 mg of IV diazepam. The most important message is you have to increase the dose of your anesthetic with the next ECT; a lower dose of anesthetic is not the solution.”

It is also important to watch for these possible complications:

• Postanesthetic shivering: This is a rare but potentially fatal complication. It’s important to be familiar with the grading system, and to recognize that grade 3 or 4 post-anesthetic shivering requires treatment. “The treatment of choice is clonidine. That should always be with you when you do ECT,” Dr. Sartorius observed.
• Cardiac arrhythmias: “ECT is a proarrhythmic intervention; don’t forget that,” he said.
• Poststimulation asystole: This occurs in more than half of treated patients. It’s caused by the current, not the seizure, and it stops within a few seconds after the current halts. If the asystoles bother the patient, try switching to bifrontal electrode placement. Right unilateral stimulation has been shown to increase the likelihood of asystole by 207-fold, compared with bifrontal stimulation.
• Tachycardia: This is another common complication of ECT. It responds well to a short-acting beta-blocker.
• Hypersalivation: The treatment of choice is glycopyrrolate, a muscarinic receptor antagonist that doesn’t cross the blood-brain barrier.

Dr. Sartorius reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Sartorius A et al. ECNP 2020, Session EDU03.02.

Adjunctive pimavanserin brought clinically meaningful improvement in patients with anxious major depressive disorder inadequately responsive to standard antidepressants alone in a post hoc analysis of the CLARITY trial, Bryan Dirks, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

This is an intriguing observation, because it’s estimated that roughly 50% of individuals with major depressive disorder (MDD) have comorbid anxiety disorders or a high level of anxiety symptoms. Moreover, anxious depression has been associated with increased risk of suicidality, high unemployment, and impaired functioning.

CLARITY was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial whose positive results for the primary outcome have been published (J Clin Psychiatry. 2019 Sep 24;80[6]:19m12928. doi: 10.4088/JCP.19m12928). Because the encouraging findings regarding pimavanserin’s impact on anxious depression came from a post hoc analysis, the results need replication. That’s ongoing in a phase 3 trial of adjunctive pimavanserin versus placebo in patients with MDD, according to Dr. Dirks, director of clinical research at Acadia Pharmaceuticals, San Diego.

The CLARITY post hoc analysis included 104 patients with baseline MDD inadequately responsive to an SSRI or a serotonin norepinephrine reuptake inhibitor and anxious depression as defined by a Hamilton Depression Rating Scale (HAMD-17) anxiety/somatization factor subscale score of 7 or more. Twenty-nine of the patients were randomized to 34 mg of adjunctive oral pimavanserin once daily, and 75 to placebo. At 5 weeks, the HAMD-17 anxiety/somatization factor score in the pimavanserin group had dropped by a mean of 5 points from a baseline of 8.8, a significantly greater effect than the 2.8-point drop in placebo-treated controls.

By week 5, the treatment response rate as defined by at least a 50% reduction in HAMD-17 total score from baseline was 55% with pimavanserin and 22% with placebo. The remission rate as indicated by a HAMD-17 total score below 7 was 24% in the pimavanserin group, compared with 5% with placebo. These results translated into an effect size of 0.78, considered by statisticians to be on the border between medium and large. Those response and remission rates in patients with anxious depression were higher with pimavanserin and lower with placebo than in the overall CLARITY trial.

The impact of adjunctive pimavanserin on top of a background SSRI or SNRI was even more pronounced in the subgroup of patients with baseline severe MDD as defined by a HAMD-17 total score of 24 or more plus an anxiety/somatization factor score of 7 or greater. Seventeen such patients were randomized to adjunctive pimavanserin, 36 to placebo. At 5 weeks, the mean HAMD total score had dropped by 17.4 points from a baseline of 27.6 in the pimavanserin group, compared with a 9.3-point reduction in controls.

“Of note, significant differences from placebo were observed as early as week 2 with pimavanserin,” Dr. Dirks said.

Pimavanserin is a novel selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors. At present pimavanserin is Food Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, but because of the drug’s unique mechanism of action it is under study for a variety of other mental disorders. Indeed, pimavanserin is now under FDA review for a possible expanded indication for treatment of dementia-related psychosis. The drug is also under study for schizophrenia as well as for MDD.

The CLARITY trial and this post hoc analysis were sponsored by Acadia Pharmaceuticals.

[email protected]

SOURCE: Dirks B. ECNP 2020. Abstract P 094.

Adjunctive pimavanserin brought clinically meaningful improvement in patients with anxious major depressive disorder inadequately responsive to standard antidepressants alone in a post hoc analysis of the CLARITY trial, Bryan Dirks, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

This is an intriguing observation, because it’s estimated that roughly 50% of individuals with major depressive disorder (MDD) have comorbid anxiety disorders or a high level of anxiety symptoms. Moreover, anxious depression has been associated with increased risk of suicidality, high unemployment, and impaired functioning.

CLARITY was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial whose positive results for the primary outcome have been published (J Clin Psychiatry. 2019 Sep 24;80[6]:19m12928. doi: 10.4088/JCP.19m12928). Because the encouraging findings regarding pimavanserin’s impact on anxious depression came from a post hoc analysis, the results need replication. That’s ongoing in a phase 3 trial of adjunctive pimavanserin versus placebo in patients with MDD, according to Dr. Dirks, director of clinical research at Acadia Pharmaceuticals, San Diego.

The CLARITY post hoc analysis included 104 patients with baseline MDD inadequately responsive to an SSRI or a serotonin norepinephrine reuptake inhibitor and anxious depression as defined by a Hamilton Depression Rating Scale (HAMD-17) anxiety/somatization factor subscale score of 7 or more. Twenty-nine of the patients were randomized to 34 mg of adjunctive oral pimavanserin once daily, and 75 to placebo. At 5 weeks, the HAMD-17 anxiety/somatization factor score in the pimavanserin group had dropped by a mean of 5 points from a baseline of 8.8, a significantly greater effect than the 2.8-point drop in placebo-treated controls.

By week 5, the treatment response rate as defined by at least a 50% reduction in HAMD-17 total score from baseline was 55% with pimavanserin and 22% with placebo. The remission rate as indicated by a HAMD-17 total score below 7 was 24% in the pimavanserin group, compared with 5% with placebo. These results translated into an effect size of 0.78, considered by statisticians to be on the border between medium and large. Those response and remission rates in patients with anxious depression were higher with pimavanserin and lower with placebo than in the overall CLARITY trial.

The impact of adjunctive pimavanserin on top of a background SSRI or SNRI was even more pronounced in the subgroup of patients with baseline severe MDD as defined by a HAMD-17 total score of 24 or more plus an anxiety/somatization factor score of 7 or greater. Seventeen such patients were randomized to adjunctive pimavanserin, 36 to placebo. At 5 weeks, the mean HAMD total score had dropped by 17.4 points from a baseline of 27.6 in the pimavanserin group, compared with a 9.3-point reduction in controls.

“Of note, significant differences from placebo were observed as early as week 2 with pimavanserin,” Dr. Dirks said.

Pimavanserin is a novel selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors. At present pimavanserin is Food Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, but because of the drug’s unique mechanism of action it is under study for a variety of other mental disorders. Indeed, pimavanserin is now under FDA review for a possible expanded indication for treatment of dementia-related psychosis. The drug is also under study for schizophrenia as well as for MDD.

The CLARITY trial and this post hoc analysis were sponsored by Acadia Pharmaceuticals.

[email protected]

SOURCE: Dirks B. ECNP 2020. Abstract P 094.

Adjunctive pimavanserin brought clinically meaningful improvement in patients with anxious major depressive disorder inadequately responsive to standard antidepressants alone in a post hoc analysis of the CLARITY trial, Bryan Dirks, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

This is an intriguing observation, because it’s estimated that roughly 50% of individuals with major depressive disorder (MDD) have comorbid anxiety disorders or a high level of anxiety symptoms. Moreover, anxious depression has been associated with increased risk of suicidality, high unemployment, and impaired functioning.

CLARITY was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial whose positive results for the primary outcome have been published (J Clin Psychiatry. 2019 Sep 24;80[6]:19m12928. doi: 10.4088/JCP.19m12928). Because the encouraging findings regarding pimavanserin’s impact on anxious depression came from a post hoc analysis, the results need replication. That’s ongoing in a phase 3 trial of adjunctive pimavanserin versus placebo in patients with MDD, according to Dr. Dirks, director of clinical research at Acadia Pharmaceuticals, San Diego.

The CLARITY post hoc analysis included 104 patients with baseline MDD inadequately responsive to an SSRI or a serotonin norepinephrine reuptake inhibitor and anxious depression as defined by a Hamilton Depression Rating Scale (HAMD-17) anxiety/somatization factor subscale score of 7 or more. Twenty-nine of the patients were randomized to 34 mg of adjunctive oral pimavanserin once daily, and 75 to placebo. At 5 weeks, the HAMD-17 anxiety/somatization factor score in the pimavanserin group had dropped by a mean of 5 points from a baseline of 8.8, a significantly greater effect than the 2.8-point drop in placebo-treated controls.

By week 5, the treatment response rate as defined by at least a 50% reduction in HAMD-17 total score from baseline was 55% with pimavanserin and 22% with placebo. The remission rate as indicated by a HAMD-17 total score below 7 was 24% in the pimavanserin group, compared with 5% with placebo. These results translated into an effect size of 0.78, considered by statisticians to be on the border between medium and large. Those response and remission rates in patients with anxious depression were higher with pimavanserin and lower with placebo than in the overall CLARITY trial.

The impact of adjunctive pimavanserin on top of a background SSRI or SNRI was even more pronounced in the subgroup of patients with baseline severe MDD as defined by a HAMD-17 total score of 24 or more plus an anxiety/somatization factor score of 7 or greater. Seventeen such patients were randomized to adjunctive pimavanserin, 36 to placebo. At 5 weeks, the mean HAMD total score had dropped by 17.4 points from a baseline of 27.6 in the pimavanserin group, compared with a 9.3-point reduction in controls.

“Of note, significant differences from placebo were observed as early as week 2 with pimavanserin,” Dr. Dirks said.

Pimavanserin is a novel selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors. At present pimavanserin is Food Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, but because of the drug’s unique mechanism of action it is under study for a variety of other mental disorders. Indeed, pimavanserin is now under FDA review for a possible expanded indication for treatment of dementia-related psychosis. The drug is also under study for schizophrenia as well as for MDD.

The CLARITY trial and this post hoc analysis were sponsored by Acadia Pharmaceuticals.

[email protected]

SOURCE: Dirks B. ECNP 2020. Abstract P 094.

Percutaneous mitral valve repair with the MitraClip appears to be a safe, effective, and life-saving new treatment for severe acute mitral regurgitation (MR) secondary to MI in surgical noncandidates, even when accompanied by cardiogenic shock, according to data from the international IREMMI registry.

“Cardiogenic shock, when adequately supported, does not seem to influence short- and mid-term outcomes, so the development of cardiogenic shock should not preclude percutaneous mitral valve repair in this scenario,” Rodrigo Estevez-Loureiro, MD, PhD, said in presenting the IREMMI (International Registry of MitraClip in Acute Myocardial Infarction) findings reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

Commentators hailed the prospective IREMMI data as potentially practice changing in light of the dire prognosis of such patients when surgery is deemed unacceptably high risk because medical management, the traditionally the only alternative, has a 30-day mortality of up to 50%.

Severe acute MR occurs in an estimated 3% of acute MIs, and in roughly 10% of patients who present with acute MI complicated by cardiogenic shock (CS). The impact of intervening with the MitraClip in an effort to correct the acute MR arising from MI with CS has previously been addressed only in sparse case reports. The new IREMMI study is easily the largest dataset to date detailing clinical and echocardiographic outcomes, Dr. Estevez-Loureiro of Alvaro Cunqueiro Hospital in Vigo, Spain, said at the meeting, sponsored by the Cardiovascular Research Foundation.

He reported on 93 consecutive patients who underwent MitraClip implantation for acute MR arising in the setting of MI, including 50 patients in CS at the time of the procedure. All 93 patients had been turned down by their surgical team because of extreme surgical risk. Three-quarters of the MIs showed ST-segment elevation. Only six patients had a papillary muscle rupture; in the rest, the mechanism of acute MR involved left ventricular global remodeling associated with mitral valve leaflet tethering. Percutaneous valve repair was performed at 18 expert valvular heart centers in the United States, Canada, Israel, and five European countries.
 

Procedural success

Time from MI to MitraClip implantation averaged 24 days in the CS patients and 33 days in the comparator arm without CS.

“These patients had been turned down for surgery, so the attending physicians generally followed a strategy of trying to cool them down with mechanical circulatory support and vasopressors. MitraClip wasn’t an option at the beginning, but after two or three failed weanings from all the possible therapies, then MitraClip becomes an option. This is one of the reasons why the time lapse between MI and the clip is so large,” the cardiologist explained.

Procedural success rates were similar in the two groups: 90% in those with CS and 93% in those without. However, average procedure time was significantly longer in the CS patients: 143 minutes versus 83 minutes in the patients without CS.

At baseline, 86% of the CS group had grade 4+ MR, similar to the 79% rate in the non-CS patients. Postprocedurally, 60% of the CS group were MR grade 0/1 and 34% were grade 2, comparable to the rates of 65% and 23% in the non-CS group.

At 3 months’ follow-up, 83.4% of the CS group had MR grade 2 or less, again not significantly different from the 90.5% rate in non-CS patients. Systolic pulmonary artery pressure was also similar: 39.6 mm Hg in the CS patients, 44 mm Hg in those without. While everyone was New York Heart Association functional class IV preprocedurally, 79.5% of the CS group were NYHA class I or II at 3 months, not significantly different from the 86.5% prevalence in the comparator arm.
 

Longer-term clinical outcomes

At a median follow-up of 7 months, the composite primary clinical outcome composed of all-cause mortality or heart failure rehospitalization did not differ between the two groups: a 28% rate in the CS group and 25.6% in non-CS patients. All-cause mortality occurred in 16% with CS and 9.3% without, again not a significant difference.

In a Cox regression analysis, neither surgical risk score, patient age, left ventricular geometry, nor CS was independently associated with the primary composite endpoint. Indeed, the only independent predictor of freedom from mortality or heart failure readmission at follow-up was procedural success, which is very much a function of the experience of the heart team, Dr. Estevez-Loureiro continued.

Michael A. Borger, MD, PhD, who comoderated the late-breaking clinical science session, was wowed by the IREMMI results.

“The mortality rates, I can tell you, compared to traditional surgical series of acute MR in the face of ACS [acute cardiogenic shock] are very, very respectable,” commented Dr. Borger, director of the cardiac surgery clinic at the Leipzig (Ger.) University Heart Center.

“Extremely impressive,” agreed discussant Vinayak N. Bapat, MD, a cardiothoracic surgeon and valve scientist at the Minneapolis Heart Institute Foundation. He posed a practical question: “Should we take from this presentation that patients should be stabilized with something like ECMO [extracorporeal membrane oxygenation] or Impella [left ventricular assist device], then transferred to an expert center for the procedure?”

“I think that the stabilization is essential in the patients with cardiogenic shock,” Dr. Estevez-Loureiro replied. “Unlike with surgery, it’s very difficult to establish a MitraClip procedure in a couple of hours in the middle of the night. You have to stabilize them and then treat for shock with ECMO, Impella, or both. I think they should be transferred to a center than can deliver the best treatment. In centers with less experience, patients can be put on mechanical support and transferred to an expert valve center, not only for MitraClip implantation, but for discussion of all the treatment possibilities, including surgery.”

At a press conference in which Dr. Estevez-Loureiro presented highlights of the IREMMI study, discussant Dee Dee Wang, MD, said the international coinvestigators “need to be applauded” for this study.

“Having these outcomes is incredible,” declared Dr. Wang, a structural heart disease specialist at the Henry Ford Health System, Detroit.

While this is an observational study, it’s a high-quality dataset with excellent methodology. And conducting a randomized trial in patients with such high surgical risk scores – the CS group had an average EuroSCORE II of 21 – would be extremely difficult, according to the cardiologist.

Dr. Estevez-Loureiro reported receiving research grants from Abbott and serving as a consultant to that company as well as Boston Scientific.
 

[email protected]

SOURCE: Estevez-Loureiro, R. TCT 2020, LBCS session IV.

Percutaneous mitral valve repair with the MitraClip appears to be a safe, effective, and life-saving new treatment for severe acute mitral regurgitation (MR) secondary to MI in surgical noncandidates, even when accompanied by cardiogenic shock, according to data from the international IREMMI registry.

“Cardiogenic shock, when adequately supported, does not seem to influence short- and mid-term outcomes, so the development of cardiogenic shock should not preclude percutaneous mitral valve repair in this scenario,” Rodrigo Estevez-Loureiro, MD, PhD, said in presenting the IREMMI (International Registry of MitraClip in Acute Myocardial Infarction) findings reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

Commentators hailed the prospective IREMMI data as potentially practice changing in light of the dire prognosis of such patients when surgery is deemed unacceptably high risk because medical management, the traditionally the only alternative, has a 30-day mortality of up to 50%.

Severe acute MR occurs in an estimated 3% of acute MIs, and in roughly 10% of patients who present with acute MI complicated by cardiogenic shock (CS). The impact of intervening with the MitraClip in an effort to correct the acute MR arising from MI with CS has previously been addressed only in sparse case reports. The new IREMMI study is easily the largest dataset to date detailing clinical and echocardiographic outcomes, Dr. Estevez-Loureiro of Alvaro Cunqueiro Hospital in Vigo, Spain, said at the meeting, sponsored by the Cardiovascular Research Foundation.

He reported on 93 consecutive patients who underwent MitraClip implantation for acute MR arising in the setting of MI, including 50 patients in CS at the time of the procedure. All 93 patients had been turned down by their surgical team because of extreme surgical risk. Three-quarters of the MIs showed ST-segment elevation. Only six patients had a papillary muscle rupture; in the rest, the mechanism of acute MR involved left ventricular global remodeling associated with mitral valve leaflet tethering. Percutaneous valve repair was performed at 18 expert valvular heart centers in the United States, Canada, Israel, and five European countries.
 

Procedural success

Time from MI to MitraClip implantation averaged 24 days in the CS patients and 33 days in the comparator arm without CS.

“These patients had been turned down for surgery, so the attending physicians generally followed a strategy of trying to cool them down with mechanical circulatory support and vasopressors. MitraClip wasn’t an option at the beginning, but after two or three failed weanings from all the possible therapies, then MitraClip becomes an option. This is one of the reasons why the time lapse between MI and the clip is so large,” the cardiologist explained.

Procedural success rates were similar in the two groups: 90% in those with CS and 93% in those without. However, average procedure time was significantly longer in the CS patients: 143 minutes versus 83 minutes in the patients without CS.

At baseline, 86% of the CS group had grade 4+ MR, similar to the 79% rate in the non-CS patients. Postprocedurally, 60% of the CS group were MR grade 0/1 and 34% were grade 2, comparable to the rates of 65% and 23% in the non-CS group.

At 3 months’ follow-up, 83.4% of the CS group had MR grade 2 or less, again not significantly different from the 90.5% rate in non-CS patients. Systolic pulmonary artery pressure was also similar: 39.6 mm Hg in the CS patients, 44 mm Hg in those without. While everyone was New York Heart Association functional class IV preprocedurally, 79.5% of the CS group were NYHA class I or II at 3 months, not significantly different from the 86.5% prevalence in the comparator arm.
 

Longer-term clinical outcomes

At a median follow-up of 7 months, the composite primary clinical outcome composed of all-cause mortality or heart failure rehospitalization did not differ between the two groups: a 28% rate in the CS group and 25.6% in non-CS patients. All-cause mortality occurred in 16% with CS and 9.3% without, again not a significant difference.

In a Cox regression analysis, neither surgical risk score, patient age, left ventricular geometry, nor CS was independently associated with the primary composite endpoint. Indeed, the only independent predictor of freedom from mortality or heart failure readmission at follow-up was procedural success, which is very much a function of the experience of the heart team, Dr. Estevez-Loureiro continued.

Michael A. Borger, MD, PhD, who comoderated the late-breaking clinical science session, was wowed by the IREMMI results.

“The mortality rates, I can tell you, compared to traditional surgical series of acute MR in the face of ACS [acute cardiogenic shock] are very, very respectable,” commented Dr. Borger, director of the cardiac surgery clinic at the Leipzig (Ger.) University Heart Center.

“Extremely impressive,” agreed discussant Vinayak N. Bapat, MD, a cardiothoracic surgeon and valve scientist at the Minneapolis Heart Institute Foundation. He posed a practical question: “Should we take from this presentation that patients should be stabilized with something like ECMO [extracorporeal membrane oxygenation] or Impella [left ventricular assist device], then transferred to an expert center for the procedure?”

“I think that the stabilization is essential in the patients with cardiogenic shock,” Dr. Estevez-Loureiro replied. “Unlike with surgery, it’s very difficult to establish a MitraClip procedure in a couple of hours in the middle of the night. You have to stabilize them and then treat for shock with ECMO, Impella, or both. I think they should be transferred to a center than can deliver the best treatment. In centers with less experience, patients can be put on mechanical support and transferred to an expert valve center, not only for MitraClip implantation, but for discussion of all the treatment possibilities, including surgery.”

At a press conference in which Dr. Estevez-Loureiro presented highlights of the IREMMI study, discussant Dee Dee Wang, MD, said the international coinvestigators “need to be applauded” for this study.

“Having these outcomes is incredible,” declared Dr. Wang, a structural heart disease specialist at the Henry Ford Health System, Detroit.

While this is an observational study, it’s a high-quality dataset with excellent methodology. And conducting a randomized trial in patients with such high surgical risk scores – the CS group had an average EuroSCORE II of 21 – would be extremely difficult, according to the cardiologist.

Dr. Estevez-Loureiro reported receiving research grants from Abbott and serving as a consultant to that company as well as Boston Scientific.
 

[email protected]

SOURCE: Estevez-Loureiro, R. TCT 2020, LBCS session IV.

Percutaneous mitral valve repair with the MitraClip appears to be a safe, effective, and life-saving new treatment for severe acute mitral regurgitation (MR) secondary to MI in surgical noncandidates, even when accompanied by cardiogenic shock, according to data from the international IREMMI registry.

“Cardiogenic shock, when adequately supported, does not seem to influence short- and mid-term outcomes, so the development of cardiogenic shock should not preclude percutaneous mitral valve repair in this scenario,” Rodrigo Estevez-Loureiro, MD, PhD, said in presenting the IREMMI (International Registry of MitraClip in Acute Myocardial Infarction) findings reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

Commentators hailed the prospective IREMMI data as potentially practice changing in light of the dire prognosis of such patients when surgery is deemed unacceptably high risk because medical management, the traditionally the only alternative, has a 30-day mortality of up to 50%.

Severe acute MR occurs in an estimated 3% of acute MIs, and in roughly 10% of patients who present with acute MI complicated by cardiogenic shock (CS). The impact of intervening with the MitraClip in an effort to correct the acute MR arising from MI with CS has previously been addressed only in sparse case reports. The new IREMMI study is easily the largest dataset to date detailing clinical and echocardiographic outcomes, Dr. Estevez-Loureiro of Alvaro Cunqueiro Hospital in Vigo, Spain, said at the meeting, sponsored by the Cardiovascular Research Foundation.

He reported on 93 consecutive patients who underwent MitraClip implantation for acute MR arising in the setting of MI, including 50 patients in CS at the time of the procedure. All 93 patients had been turned down by their surgical team because of extreme surgical risk. Three-quarters of the MIs showed ST-segment elevation. Only six patients had a papillary muscle rupture; in the rest, the mechanism of acute MR involved left ventricular global remodeling associated with mitral valve leaflet tethering. Percutaneous valve repair was performed at 18 expert valvular heart centers in the United States, Canada, Israel, and five European countries.
 

Procedural success

Time from MI to MitraClip implantation averaged 24 days in the CS patients and 33 days in the comparator arm without CS.

“These patients had been turned down for surgery, so the attending physicians generally followed a strategy of trying to cool them down with mechanical circulatory support and vasopressors. MitraClip wasn’t an option at the beginning, but after two or three failed weanings from all the possible therapies, then MitraClip becomes an option. This is one of the reasons why the time lapse between MI and the clip is so large,” the cardiologist explained.

Procedural success rates were similar in the two groups: 90% in those with CS and 93% in those without. However, average procedure time was significantly longer in the CS patients: 143 minutes versus 83 minutes in the patients without CS.

At baseline, 86% of the CS group had grade 4+ MR, similar to the 79% rate in the non-CS patients. Postprocedurally, 60% of the CS group were MR grade 0/1 and 34% were grade 2, comparable to the rates of 65% and 23% in the non-CS group.

At 3 months’ follow-up, 83.4% of the CS group had MR grade 2 or less, again not significantly different from the 90.5% rate in non-CS patients. Systolic pulmonary artery pressure was also similar: 39.6 mm Hg in the CS patients, 44 mm Hg in those without. While everyone was New York Heart Association functional class IV preprocedurally, 79.5% of the CS group were NYHA class I or II at 3 months, not significantly different from the 86.5% prevalence in the comparator arm.
 

Longer-term clinical outcomes

At a median follow-up of 7 months, the composite primary clinical outcome composed of all-cause mortality or heart failure rehospitalization did not differ between the two groups: a 28% rate in the CS group and 25.6% in non-CS patients. All-cause mortality occurred in 16% with CS and 9.3% without, again not a significant difference.

In a Cox regression analysis, neither surgical risk score, patient age, left ventricular geometry, nor CS was independently associated with the primary composite endpoint. Indeed, the only independent predictor of freedom from mortality or heart failure readmission at follow-up was procedural success, which is very much a function of the experience of the heart team, Dr. Estevez-Loureiro continued.

Michael A. Borger, MD, PhD, who comoderated the late-breaking clinical science session, was wowed by the IREMMI results.

“The mortality rates, I can tell you, compared to traditional surgical series of acute MR in the face of ACS [acute cardiogenic shock] are very, very respectable,” commented Dr. Borger, director of the cardiac surgery clinic at the Leipzig (Ger.) University Heart Center.

“Extremely impressive,” agreed discussant Vinayak N. Bapat, MD, a cardiothoracic surgeon and valve scientist at the Minneapolis Heart Institute Foundation. He posed a practical question: “Should we take from this presentation that patients should be stabilized with something like ECMO [extracorporeal membrane oxygenation] or Impella [left ventricular assist device], then transferred to an expert center for the procedure?”

“I think that the stabilization is essential in the patients with cardiogenic shock,” Dr. Estevez-Loureiro replied. “Unlike with surgery, it’s very difficult to establish a MitraClip procedure in a couple of hours in the middle of the night. You have to stabilize them and then treat for shock with ECMO, Impella, or both. I think they should be transferred to a center than can deliver the best treatment. In centers with less experience, patients can be put on mechanical support and transferred to an expert valve center, not only for MitraClip implantation, but for discussion of all the treatment possibilities, including surgery.”

At a press conference in which Dr. Estevez-Loureiro presented highlights of the IREMMI study, discussant Dee Dee Wang, MD, said the international coinvestigators “need to be applauded” for this study.

“Having these outcomes is incredible,” declared Dr. Wang, a structural heart disease specialist at the Henry Ford Health System, Detroit.

While this is an observational study, it’s a high-quality dataset with excellent methodology. And conducting a randomized trial in patients with such high surgical risk scores – the CS group had an average EuroSCORE II of 21 – would be extremely difficult, according to the cardiologist.

Dr. Estevez-Loureiro reported receiving research grants from Abbott and serving as a consultant to that company as well as Boston Scientific.
 

[email protected]

SOURCE: Estevez-Loureiro, R. TCT 2020, LBCS session IV.

Interleukin-23 optimizes antimicrobial macrophage activity, which is reduced among persons harboring an IL-23 receptor variant that helps protect against inflammatory bowel disease (IBD), recent research has found.

“These [findings] highlight that the susceptibility to infections with therapeutic blockade of the IL-23/IL-12 pathways may be owing in part to the essential role for IL-23 in mediating antimicrobial functions in macrophages. They further highlight that carriers of the IL-23R–Q381 variant, who are relatively protected from IBD and other immune-mediated diseases, may be at increased risk for bacterial infection,” Rui Sun and Clara Abraham, MD, of Yale University, New Haven, Conn., wrote in Cellular and Molecular Gastroenterology and Hepatology.

IL-23 is key to the pathogenesis of IBD and is being studied as a therapeutic target, both alone and in combination with IL-12 blocking. Although human macrophages express low levels of IL-23 receptor, recent research reveals that IL-23R is up-regulated “within minutes of exposure to IL-23,” which promotes signaling and cytokine secretion, the investigators wrote. However, the extent to which IL-23 supports macrophage antimicrobial activity was unknown. To characterize protein expression, signaling, and bacterial uptake and clearance of bacteria by human macrophages derived from monocytes, the investigators tested these cells with Western blot, flow cytometry, and gentamicin protection, which involved coculturing human macrophages with bacteria, adding gentamicin solution, and then lysing and plating the cells onto agar to assess the extent to which the macrophages had taken up the bacteria.

After 48 hours of exposure to IL-23 or IL-12, macrophages increased their intracellular clearance of clinically relevant bacteria, including Enterococcus faecalis, adherent invasive Escherichia coli, and Salmonella typhimurium. Notably, this did not occur when the investigators reduced (“knocked down”) macrophage expression of either IL-23R or IL-12 receptor alpha 2. Additional investigations showed that in macrophages, IL-23 promotes bacterial uptake, clearance, and autophagy by inducing a pyruvate dehydrogenase kinase 1 (PDK1)–dependent pathway mediated by Janus kinase 2/tyrosine kinase 2 and by inducing reactive oxygen species (ROS) and reactive nitrogen species (RNS) pathways. IL-23 also activates two key proteins involved in autophagy (ATG5 and ATG16L1), the researchers reported. “ROS, RNS, and autophagy cooperate to mediate IL-23-induced bacterial clearance. Reduction of each ROS, RNS, and autophagy pathway partially reversed the enhanced bacterial clearance observed with chronic IL-23 treatment.”

Further tests found that IL-23 mediates antimicrobial pathways through the Janus kinase 2, tyrosine kinase 2, and STAT3 pathways, which “cooperate to mediate optimal IL-23-induced intracellular bacterial clearance in human macrophages.” Importantly, human macrophages showed less antimicrobial activity when transfected with the IL-23R–Q381 variant than with IL-23R–R381. The IL-23R-Q381 variant, which reduces susceptibility to IBD, “decreased IL-23-induced and NOD2-induced antimicrobial pathways and intracellular bacterial clearance in monocyte-derived macrophages,” the researchers explained. Evaluating actual carriers of these variants showed the same results – macrophages harboring IBD-protective IL-23R–R381/Q381 exhibited lower antimicrobial activity and less intracellular bacterial clearance compared with macrophages from carriers of IL-23R–R381/R381.

“Taken together, IL-23 promotes increased bacterial uptake and then induces a more rapid and effective clearance of these intracellular bacteria in human monocyte-derived macrophages,” the researchers wrote. “The reduced inflammatory responses observed in IL-23R Q381 carriers are associated with protection from multiple immune-mediated diseases. This would imply that loss-of-function observed with the common IL-23R–R381Q variant may lead to a disadvantage in select infectious diseases, including through [this variant’s] now identified role in promoting antimicrobial pathways in macrophages.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SOURCE: Sun R, Abraham C. Cell Molec Gastro Hepatol. 2020 May 28. doi.: 10.1016/j.jcmgh.2020.05.007.

Interleukin-23 optimizes antimicrobial macrophage activity, which is reduced among persons harboring an IL-23 receptor variant that helps protect against inflammatory bowel disease (IBD), recent research has found.

“These [findings] highlight that the susceptibility to infections with therapeutic blockade of the IL-23/IL-12 pathways may be owing in part to the essential role for IL-23 in mediating antimicrobial functions in macrophages. They further highlight that carriers of the IL-23R–Q381 variant, who are relatively protected from IBD and other immune-mediated diseases, may be at increased risk for bacterial infection,” Rui Sun and Clara Abraham, MD, of Yale University, New Haven, Conn., wrote in Cellular and Molecular Gastroenterology and Hepatology.

IL-23 is key to the pathogenesis of IBD and is being studied as a therapeutic target, both alone and in combination with IL-12 blocking. Although human macrophages express low levels of IL-23 receptor, recent research reveals that IL-23R is up-regulated “within minutes of exposure to IL-23,” which promotes signaling and cytokine secretion, the investigators wrote. However, the extent to which IL-23 supports macrophage antimicrobial activity was unknown. To characterize protein expression, signaling, and bacterial uptake and clearance of bacteria by human macrophages derived from monocytes, the investigators tested these cells with Western blot, flow cytometry, and gentamicin protection, which involved coculturing human macrophages with bacteria, adding gentamicin solution, and then lysing and plating the cells onto agar to assess the extent to which the macrophages had taken up the bacteria.

After 48 hours of exposure to IL-23 or IL-12, macrophages increased their intracellular clearance of clinically relevant bacteria, including Enterococcus faecalis, adherent invasive Escherichia coli, and Salmonella typhimurium. Notably, this did not occur when the investigators reduced (“knocked down”) macrophage expression of either IL-23R or IL-12 receptor alpha 2. Additional investigations showed that in macrophages, IL-23 promotes bacterial uptake, clearance, and autophagy by inducing a pyruvate dehydrogenase kinase 1 (PDK1)–dependent pathway mediated by Janus kinase 2/tyrosine kinase 2 and by inducing reactive oxygen species (ROS) and reactive nitrogen species (RNS) pathways. IL-23 also activates two key proteins involved in autophagy (ATG5 and ATG16L1), the researchers reported. “ROS, RNS, and autophagy cooperate to mediate IL-23-induced bacterial clearance. Reduction of each ROS, RNS, and autophagy pathway partially reversed the enhanced bacterial clearance observed with chronic IL-23 treatment.”

Further tests found that IL-23 mediates antimicrobial pathways through the Janus kinase 2, tyrosine kinase 2, and STAT3 pathways, which “cooperate to mediate optimal IL-23-induced intracellular bacterial clearance in human macrophages.” Importantly, human macrophages showed less antimicrobial activity when transfected with the IL-23R–Q381 variant than with IL-23R–R381. The IL-23R-Q381 variant, which reduces susceptibility to IBD, “decreased IL-23-induced and NOD2-induced antimicrobial pathways and intracellular bacterial clearance in monocyte-derived macrophages,” the researchers explained. Evaluating actual carriers of these variants showed the same results – macrophages harboring IBD-protective IL-23R–R381/Q381 exhibited lower antimicrobial activity and less intracellular bacterial clearance compared with macrophages from carriers of IL-23R–R381/R381.

“Taken together, IL-23 promotes increased bacterial uptake and then induces a more rapid and effective clearance of these intracellular bacteria in human monocyte-derived macrophages,” the researchers wrote. “The reduced inflammatory responses observed in IL-23R Q381 carriers are associated with protection from multiple immune-mediated diseases. This would imply that loss-of-function observed with the common IL-23R–R381Q variant may lead to a disadvantage in select infectious diseases, including through [this variant’s] now identified role in promoting antimicrobial pathways in macrophages.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SOURCE: Sun R, Abraham C. Cell Molec Gastro Hepatol. 2020 May 28. doi.: 10.1016/j.jcmgh.2020.05.007.

Interleukin-23 optimizes antimicrobial macrophage activity, which is reduced among persons harboring an IL-23 receptor variant that helps protect against inflammatory bowel disease (IBD), recent research has found.

“These [findings] highlight that the susceptibility to infections with therapeutic blockade of the IL-23/IL-12 pathways may be owing in part to the essential role for IL-23 in mediating antimicrobial functions in macrophages. They further highlight that carriers of the IL-23R–Q381 variant, who are relatively protected from IBD and other immune-mediated diseases, may be at increased risk for bacterial infection,” Rui Sun and Clara Abraham, MD, of Yale University, New Haven, Conn., wrote in Cellular and Molecular Gastroenterology and Hepatology.

IL-23 is key to the pathogenesis of IBD and is being studied as a therapeutic target, both alone and in combination with IL-12 blocking. Although human macrophages express low levels of IL-23 receptor, recent research reveals that IL-23R is up-regulated “within minutes of exposure to IL-23,” which promotes signaling and cytokine secretion, the investigators wrote. However, the extent to which IL-23 supports macrophage antimicrobial activity was unknown. To characterize protein expression, signaling, and bacterial uptake and clearance of bacteria by human macrophages derived from monocytes, the investigators tested these cells with Western blot, flow cytometry, and gentamicin protection, which involved coculturing human macrophages with bacteria, adding gentamicin solution, and then lysing and plating the cells onto agar to assess the extent to which the macrophages had taken up the bacteria.

After 48 hours of exposure to IL-23 or IL-12, macrophages increased their intracellular clearance of clinically relevant bacteria, including Enterococcus faecalis, adherent invasive Escherichia coli, and Salmonella typhimurium. Notably, this did not occur when the investigators reduced (“knocked down”) macrophage expression of either IL-23R or IL-12 receptor alpha 2. Additional investigations showed that in macrophages, IL-23 promotes bacterial uptake, clearance, and autophagy by inducing a pyruvate dehydrogenase kinase 1 (PDK1)–dependent pathway mediated by Janus kinase 2/tyrosine kinase 2 and by inducing reactive oxygen species (ROS) and reactive nitrogen species (RNS) pathways. IL-23 also activates two key proteins involved in autophagy (ATG5 and ATG16L1), the researchers reported. “ROS, RNS, and autophagy cooperate to mediate IL-23-induced bacterial clearance. Reduction of each ROS, RNS, and autophagy pathway partially reversed the enhanced bacterial clearance observed with chronic IL-23 treatment.”

Further tests found that IL-23 mediates antimicrobial pathways through the Janus kinase 2, tyrosine kinase 2, and STAT3 pathways, which “cooperate to mediate optimal IL-23-induced intracellular bacterial clearance in human macrophages.” Importantly, human macrophages showed less antimicrobial activity when transfected with the IL-23R–Q381 variant than with IL-23R–R381. The IL-23R-Q381 variant, which reduces susceptibility to IBD, “decreased IL-23-induced and NOD2-induced antimicrobial pathways and intracellular bacterial clearance in monocyte-derived macrophages,” the researchers explained. Evaluating actual carriers of these variants showed the same results – macrophages harboring IBD-protective IL-23R–R381/Q381 exhibited lower antimicrobial activity and less intracellular bacterial clearance compared with macrophages from carriers of IL-23R–R381/R381.

“Taken together, IL-23 promotes increased bacterial uptake and then induces a more rapid and effective clearance of these intracellular bacteria in human monocyte-derived macrophages,” the researchers wrote. “The reduced inflammatory responses observed in IL-23R Q381 carriers are associated with protection from multiple immune-mediated diseases. This would imply that loss-of-function observed with the common IL-23R–R381Q variant may lead to a disadvantage in select infectious diseases, including through [this variant’s] now identified role in promoting antimicrobial pathways in macrophages.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SOURCE: Sun R, Abraham C. Cell Molec Gastro Hepatol. 2020 May 28. doi.: 10.1016/j.jcmgh.2020.05.007.

Intravascular lithotripsy proved highly effective, safe, and user friendly as an adjunct to stenting for severely calcified coronary lesions at 30 days of follow-up in the pivotal Disrupt CAD III study aimed at gaining U.S. regulatory approval.

The technology is basically the same as in extracorporeal lithotripsy, used for the treatment of kidney stones for more than 30 years: namely, transmission of pulsed acoustic pressure waves in order to fracture calcium. For interventional cardiology purposes, however, the transmitter is located within a balloon angioplasty catheter, Dean J. Kereiakes, MD, explained in presenting the study results at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

In Disrupt CAD III, intravascular lithotripsy far exceeded the procedural success and 30-day freedom from major adverse cardiovascular event (MACE) performance targets set in conjunction with the Food and Drug Administration. In so doing, the intravascular lithotripsy device developed by Shockwave Medical successfully addressed one of the banes of contemporary interventional cardiology: heavily calcified coronary lesions.

Currently available technologies targeting such lesions, including noncompliant high-pressure balloons, intravascular lasers, cutting balloons, and orbital and rotational atherectomy, often yield suboptimal results, noted Dr. Kereiakes, medical director of the Christ Hospital Heart and Cardiovascular Center in Cincinnati.

Severe vascular calcifications are becoming more common, due in part to an aging population and the growing prevalence of hypertension, diabetes, and renal insufficiency. Severely calcified coronary lesions complicate percutaneous coronary intervention. They’re associated with increased risks of dissection, perforation, and periprocedural MI. Moreover, heavily calcified lesions impede stent delivery and expansion – and stent underexpansion is the leading predictor of restenosis and stent thrombosis, he observed at the meeting, sponsored by the Cardiovascular Research Foundation. Disrupt CAD III was a prospective single-arm study of 384 patients at 47 sites in the United States and several European countries. All participants had de novo coronary calcifications graded as severe by core laboratory assessment, with a mean calcified length of 47.9 mm by quantitative coronary angiography and a mean calcium angle and thickness of 292.5 degrees and 0.96 mm by optical coherence tomography.

“It’s staggering, the level of calcification these patients had. It’s jaw dropping,” Dr. Kereiakes observed.

Intravascular lithotripsy was used to prepare these severely calcified lesions for stenting. The intervention entailed transmission of acoustic waves circumferentially and transmurally at 1 pulse per second through tissue at an effective pressure of about 50 atm. Patients received an average of 69 pulses.

This was not a randomized trial; there was no sham-treated control arm. Instead, the comparator group selected under regulatory guidance was comprised of patients who had received orbital atherectomy for severe coronary calcifications in the earlier, similarly designed ORBIT II trial, which led to FDA marketing approval of that technology.

Key outcomes

The procedural success rate, defined as successful stent delivery with less than a 50% residual stenosis and no in-hospital MACE, was 92.4% in Disrupt CAD III, compared to 83.4% for orbital atherectomy in ORBIT II. The primary safety endpoint of freedom from cardiac death, MI, or target vessel revascularization at 30 days was achieved in 92.2% of patients in the intravascular lithotripsy trial, versus 84.4% in ORBIT II.

The 30-day MACE rate of 7.8% in Disrupt CAD III was primarily driven by periprocedural MIs, which occurred in 6.8% of participants. Only one-third of the MIs were clinically relevant by the Society for Coronary Angiography and Intervention definition. There were two cardiac deaths and three cases of stent thrombosis, all of which were associated with known predictors of the complication. There was 1 case each of dissection, abrupt closure, and perforation, but no instances of slow flow or no reflow at the procedure’s end. Transient lithotripsy-induced left ventricular capture occurred in 41% of patients, but they were benign events with no lasting consequences.

The device was able to cross and deliver acoustic pressure wave therapy to 98.2% of lesions. The mean diameter stenosis preprocedure was 65.1%, dropping to 37.2% post lithotripsy, with a final in-stent residual stenosis diameter of 11.9%, with a 1.7-mm acute gain. The average stent expansion at the site of maximum calcification was 102%, with a minimum stent area of 6.5 mm².

Optical coherence imaging revealed that 67% of treated lesions had circumferential and transmural fractures of both deep and superficial calcium post lithotripsy. Yet outcomes were the same regardless of whether fractures were evident on imaging.

At 30-day follow-up, 72.9% of patients had no angina, up from just 12.6% of participants pre-PCI. Follow-up will continue for 2 years.

Outcomes were similar for the first case done at each participating center and all cases thereafter.

“The ease of use was remarkable,” Dr. Kereiakes recalled. “The learning curve is virtually nonexistent.”
 

The reaction

At a press conference where Dr. Kereiakes presented the Disrupt CAD III results, discussant Allen Jeremias, MD, said he found the results compelling.

“The success rate is high, I think it’s relatively easy to use, as demonstrated, and I think the results are spectacular,” said Dr. Jeremias, director of interventional cardiology research and associate director of the cardiac catheterization laboratory at St. Francis Hospital in Roslyn, N.Y.

Bruce Jancin/MDedge News

[email protected]

SOURCE: Kereiakes DJ. TCT 2020. Late Breaking Clinical Science session 2.

Intravascular lithotripsy proved highly effective, safe, and user friendly as an adjunct to stenting for severely calcified coronary lesions at 30 days of follow-up in the pivotal Disrupt CAD III study aimed at gaining U.S. regulatory approval.

The technology is basically the same as in extracorporeal lithotripsy, used for the treatment of kidney stones for more than 30 years: namely, transmission of pulsed acoustic pressure waves in order to fracture calcium. For interventional cardiology purposes, however, the transmitter is located within a balloon angioplasty catheter, Dean J. Kereiakes, MD, explained in presenting the study results at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

In Disrupt CAD III, intravascular lithotripsy far exceeded the procedural success and 30-day freedom from major adverse cardiovascular event (MACE) performance targets set in conjunction with the Food and Drug Administration. In so doing, the intravascular lithotripsy device developed by Shockwave Medical successfully addressed one of the banes of contemporary interventional cardiology: heavily calcified coronary lesions.

Currently available technologies targeting such lesions, including noncompliant high-pressure balloons, intravascular lasers, cutting balloons, and orbital and rotational atherectomy, often yield suboptimal results, noted Dr. Kereiakes, medical director of the Christ Hospital Heart and Cardiovascular Center in Cincinnati.

Severe vascular calcifications are becoming more common, due in part to an aging population and the growing prevalence of hypertension, diabetes, and renal insufficiency. Severely calcified coronary lesions complicate percutaneous coronary intervention. They’re associated with increased risks of dissection, perforation, and periprocedural MI. Moreover, heavily calcified lesions impede stent delivery and expansion – and stent underexpansion is the leading predictor of restenosis and stent thrombosis, he observed at the meeting, sponsored by the Cardiovascular Research Foundation. Disrupt CAD III was a prospective single-arm study of 384 patients at 47 sites in the United States and several European countries. All participants had de novo coronary calcifications graded as severe by core laboratory assessment, with a mean calcified length of 47.9 mm by quantitative coronary angiography and a mean calcium angle and thickness of 292.5 degrees and 0.96 mm by optical coherence tomography.

“It’s staggering, the level of calcification these patients had. It’s jaw dropping,” Dr. Kereiakes observed.

Intravascular lithotripsy was used to prepare these severely calcified lesions for stenting. The intervention entailed transmission of acoustic waves circumferentially and transmurally at 1 pulse per second through tissue at an effective pressure of about 50 atm. Patients received an average of 69 pulses.

This was not a randomized trial; there was no sham-treated control arm. Instead, the comparator group selected under regulatory guidance was comprised of patients who had received orbital atherectomy for severe coronary calcifications in the earlier, similarly designed ORBIT II trial, which led to FDA marketing approval of that technology.

Key outcomes

The procedural success rate, defined as successful stent delivery with less than a 50% residual stenosis and no in-hospital MACE, was 92.4% in Disrupt CAD III, compared to 83.4% for orbital atherectomy in ORBIT II. The primary safety endpoint of freedom from cardiac death, MI, or target vessel revascularization at 30 days was achieved in 92.2% of patients in the intravascular lithotripsy trial, versus 84.4% in ORBIT II.

The 30-day MACE rate of 7.8% in Disrupt CAD III was primarily driven by periprocedural MIs, which occurred in 6.8% of participants. Only one-third of the MIs were clinically relevant by the Society for Coronary Angiography and Intervention definition. There were two cardiac deaths and three cases of stent thrombosis, all of which were associated with known predictors of the complication. There was 1 case each of dissection, abrupt closure, and perforation, but no instances of slow flow or no reflow at the procedure’s end. Transient lithotripsy-induced left ventricular capture occurred in 41% of patients, but they were benign events with no lasting consequences.

The device was able to cross and deliver acoustic pressure wave therapy to 98.2% of lesions. The mean diameter stenosis preprocedure was 65.1%, dropping to 37.2% post lithotripsy, with a final in-stent residual stenosis diameter of 11.9%, with a 1.7-mm acute gain. The average stent expansion at the site of maximum calcification was 102%, with a minimum stent area of 6.5 mm².

Optical coherence imaging revealed that 67% of treated lesions had circumferential and transmural fractures of both deep and superficial calcium post lithotripsy. Yet outcomes were the same regardless of whether fractures were evident on imaging.

At 30-day follow-up, 72.9% of patients had no angina, up from just 12.6% of participants pre-PCI. Follow-up will continue for 2 years.

Outcomes were similar for the first case done at each participating center and all cases thereafter.

“The ease of use was remarkable,” Dr. Kereiakes recalled. “The learning curve is virtually nonexistent.”
 

The reaction

At a press conference where Dr. Kereiakes presented the Disrupt CAD III results, discussant Allen Jeremias, MD, said he found the results compelling.

“The success rate is high, I think it’s relatively easy to use, as demonstrated, and I think the results are spectacular,” said Dr. Jeremias, director of interventional cardiology research and associate director of the cardiac catheterization laboratory at St. Francis Hospital in Roslyn, N.Y.

Bruce Jancin/MDedge News

[email protected]

SOURCE: Kereiakes DJ. TCT 2020. Late Breaking Clinical Science session 2.

Intravascular lithotripsy proved highly effective, safe, and user friendly as an adjunct to stenting for severely calcified coronary lesions at 30 days of follow-up in the pivotal Disrupt CAD III study aimed at gaining U.S. regulatory approval.

The technology is basically the same as in extracorporeal lithotripsy, used for the treatment of kidney stones for more than 30 years: namely, transmission of pulsed acoustic pressure waves in order to fracture calcium. For interventional cardiology purposes, however, the transmitter is located within a balloon angioplasty catheter, Dean J. Kereiakes, MD, explained in presenting the study results at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

In Disrupt CAD III, intravascular lithotripsy far exceeded the procedural success and 30-day freedom from major adverse cardiovascular event (MACE) performance targets set in conjunction with the Food and Drug Administration. In so doing, the intravascular lithotripsy device developed by Shockwave Medical successfully addressed one of the banes of contemporary interventional cardiology: heavily calcified coronary lesions.

Currently available technologies targeting such lesions, including noncompliant high-pressure balloons, intravascular lasers, cutting balloons, and orbital and rotational atherectomy, often yield suboptimal results, noted Dr. Kereiakes, medical director of the Christ Hospital Heart and Cardiovascular Center in Cincinnati.

Severe vascular calcifications are becoming more common, due in part to an aging population and the growing prevalence of hypertension, diabetes, and renal insufficiency. Severely calcified coronary lesions complicate percutaneous coronary intervention. They’re associated with increased risks of dissection, perforation, and periprocedural MI. Moreover, heavily calcified lesions impede stent delivery and expansion – and stent underexpansion is the leading predictor of restenosis and stent thrombosis, he observed at the meeting, sponsored by the Cardiovascular Research Foundation. Disrupt CAD III was a prospective single-arm study of 384 patients at 47 sites in the United States and several European countries. All participants had de novo coronary calcifications graded as severe by core laboratory assessment, with a mean calcified length of 47.9 mm by quantitative coronary angiography and a mean calcium angle and thickness of 292.5 degrees and 0.96 mm by optical coherence tomography.

“It’s staggering, the level of calcification these patients had. It’s jaw dropping,” Dr. Kereiakes observed.

Intravascular lithotripsy was used to prepare these severely calcified lesions for stenting. The intervention entailed transmission of acoustic waves circumferentially and transmurally at 1 pulse per second through tissue at an effective pressure of about 50 atm. Patients received an average of 69 pulses.

This was not a randomized trial; there was no sham-treated control arm. Instead, the comparator group selected under regulatory guidance was comprised of patients who had received orbital atherectomy for severe coronary calcifications in the earlier, similarly designed ORBIT II trial, which led to FDA marketing approval of that technology.

Key outcomes

The procedural success rate, defined as successful stent delivery with less than a 50% residual stenosis and no in-hospital MACE, was 92.4% in Disrupt CAD III, compared to 83.4% for orbital atherectomy in ORBIT II. The primary safety endpoint of freedom from cardiac death, MI, or target vessel revascularization at 30 days was achieved in 92.2% of patients in the intravascular lithotripsy trial, versus 84.4% in ORBIT II.

The 30-day MACE rate of 7.8% in Disrupt CAD III was primarily driven by periprocedural MIs, which occurred in 6.8% of participants. Only one-third of the MIs were clinically relevant by the Society for Coronary Angiography and Intervention definition. There were two cardiac deaths and three cases of stent thrombosis, all of which were associated with known predictors of the complication. There was 1 case each of dissection, abrupt closure, and perforation, but no instances of slow flow or no reflow at the procedure’s end. Transient lithotripsy-induced left ventricular capture occurred in 41% of patients, but they were benign events with no lasting consequences.

The device was able to cross and deliver acoustic pressure wave therapy to 98.2% of lesions. The mean diameter stenosis preprocedure was 65.1%, dropping to 37.2% post lithotripsy, with a final in-stent residual stenosis diameter of 11.9%, with a 1.7-mm acute gain. The average stent expansion at the site of maximum calcification was 102%, with a minimum stent area of 6.5 mm².

Optical coherence imaging revealed that 67% of treated lesions had circumferential and transmural fractures of both deep and superficial calcium post lithotripsy. Yet outcomes were the same regardless of whether fractures were evident on imaging.

At 30-day follow-up, 72.9% of patients had no angina, up from just 12.6% of participants pre-PCI. Follow-up will continue for 2 years.

Outcomes were similar for the first case done at each participating center and all cases thereafter.

“The ease of use was remarkable,” Dr. Kereiakes recalled. “The learning curve is virtually nonexistent.”
 

The reaction

At a press conference where Dr. Kereiakes presented the Disrupt CAD III results, discussant Allen Jeremias, MD, said he found the results compelling.

“The success rate is high, I think it’s relatively easy to use, as demonstrated, and I think the results are spectacular,” said Dr. Jeremias, director of interventional cardiology research and associate director of the cardiac catheterization laboratory at St. Francis Hospital in Roslyn, N.Y.

Bruce Jancin/MDedge News

[email protected]

SOURCE: Kereiakes DJ. TCT 2020. Late Breaking Clinical Science session 2.

To the Editor:

Paraneoplastic pemphigus (PNP), also known as paraneoplastic autoimmune multiorgan syndrome, is an autoimmune mucocutaneous blistering disease that typically occurs secondary to a lymphoproliferative disorder. Paraneoplastic pemphigus is characterized by severe erosive stomatitis, polymorphous skin lesions, and potential bronchiolitis obliterans that can mimic a wide array of conditions. The exact pathogenesis is unknown but is thought to be due to a combination of humoral and cell-mediated immunity. The condition usually confers a poor prognosis, with morbidity from 38% to upwards of 90%.¹

A 47-year-old man developed prominent pink to dusky, ill-defined, targetoid, coalescing papules over the back; violaceous macules over the palms and soles; and numerous crusted oral erosions while hospitalized for an infection. He had a history of stage IVB follicular lymphoma (double-hit type immunoglobulin heavy chain/BCL2 fusion and rearrangement of BCL6) complicated by extensive erosive skin lesions and multiple lines of infections. The clinical differential diagnosis included Stevens-Johnson syndrome vs erythema multiforme (EM) major secondary to administration of oxacillin vs PNP. Herpes simplex virus polymerase chain reaction and Mycoplasma titers were negative. Skin biopsies from the back and right abdomen revealed severe lichenoid interface dermatitis (IFD) with numerous dyskeratotic cells mimicking EM and eosinophils; however, direct immunofluorescence of the abdomen biopsy revealed an apparent suprabasal acantholysis with intercellular C3 in the lower half of the epidermis. Histologically, PNP was favored, but indirect immunofluorescence with monkey esophagus IgG was negative.

The skin lesions progressed, and an additional skin biopsy from the left arm performed 1 month later revealed similar histologic features with intercellular IgG and C3 in the lower half of the epidermis with weak basement membrane C3 (Figure 1). Serology also confirmed elevated serum antidesmoglein 1 and 3 antibodies. Thus, in the clinical setting of an erosive mucositis with EM-like and pemphigoidlike eruptions associated with B-cell lymphoma, the patient was diagnosed with PNP.

Although antidesmoglein 3 antibody was shown to be a pathologic driver in PNP, there is a weak correlation between antibody profiles and clinical presentation.⁸ In one case of PNP, antidesmoglein 3 antibody was negative, suggesting that lichenoid IFD may cause the phenotypic findings in PNP.⁹ Thus, the development of nail scarring in PNP may be explained by the presence of lichenoid IFD that is characteristic of PNP. However, the variation in antibody profile in PNP likely is a consequence of epitope spreading.

To the Editor:

Paraneoplastic pemphigus (PNP), also known as paraneoplastic autoimmune multiorgan syndrome, is an autoimmune mucocutaneous blistering disease that typically occurs secondary to a lymphoproliferative disorder. Paraneoplastic pemphigus is characterized by severe erosive stomatitis, polymorphous skin lesions, and potential bronchiolitis obliterans that can mimic a wide array of conditions. The exact pathogenesis is unknown but is thought to be due to a combination of humoral and cell-mediated immunity. The condition usually confers a poor prognosis, with morbidity from 38% to upwards of 90%.¹

A 47-year-old man developed prominent pink to dusky, ill-defined, targetoid, coalescing papules over the back; violaceous macules over the palms and soles; and numerous crusted oral erosions while hospitalized for an infection. He had a history of stage IVB follicular lymphoma (double-hit type immunoglobulin heavy chain/BCL2 fusion and rearrangement of BCL6) complicated by extensive erosive skin lesions and multiple lines of infections. The clinical differential diagnosis included Stevens-Johnson syndrome vs erythema multiforme (EM) major secondary to administration of oxacillin vs PNP. Herpes simplex virus polymerase chain reaction and Mycoplasma titers were negative. Skin biopsies from the back and right abdomen revealed severe lichenoid interface dermatitis (IFD) with numerous dyskeratotic cells mimicking EM and eosinophils; however, direct immunofluorescence of the abdomen biopsy revealed an apparent suprabasal acantholysis with intercellular C3 in the lower half of the epidermis. Histologically, PNP was favored, but indirect immunofluorescence with monkey esophagus IgG was negative.

The skin lesions progressed, and an additional skin biopsy from the left arm performed 1 month later revealed similar histologic features with intercellular IgG and C3 in the lower half of the epidermis with weak basement membrane C3 (Figure 1). Serology also confirmed elevated serum antidesmoglein 1 and 3 antibodies. Thus, in the clinical setting of an erosive mucositis with EM-like and pemphigoidlike eruptions associated with B-cell lymphoma, the patient was diagnosed with PNP.

Although antidesmoglein 3 antibody was shown to be a pathologic driver in PNP, there is a weak correlation between antibody profiles and clinical presentation.⁸ In one case of PNP, antidesmoglein 3 antibody was negative, suggesting that lichenoid IFD may cause the phenotypic findings in PNP.⁹ Thus, the development of nail scarring in PNP may be explained by the presence of lichenoid IFD that is characteristic of PNP. However, the variation in antibody profile in PNP likely is a consequence of epitope spreading.

To the Editor:

Paraneoplastic pemphigus (PNP), also known as paraneoplastic autoimmune multiorgan syndrome, is an autoimmune mucocutaneous blistering disease that typically occurs secondary to a lymphoproliferative disorder. Paraneoplastic pemphigus is characterized by severe erosive stomatitis, polymorphous skin lesions, and potential bronchiolitis obliterans that can mimic a wide array of conditions. The exact pathogenesis is unknown but is thought to be due to a combination of humoral and cell-mediated immunity. The condition usually confers a poor prognosis, with morbidity from 38% to upwards of 90%.¹

A 47-year-old man developed prominent pink to dusky, ill-defined, targetoid, coalescing papules over the back; violaceous macules over the palms and soles; and numerous crusted oral erosions while hospitalized for an infection. He had a history of stage IVB follicular lymphoma (double-hit type immunoglobulin heavy chain/BCL2 fusion and rearrangement of BCL6) complicated by extensive erosive skin lesions and multiple lines of infections. The clinical differential diagnosis included Stevens-Johnson syndrome vs erythema multiforme (EM) major secondary to administration of oxacillin vs PNP. Herpes simplex virus polymerase chain reaction and Mycoplasma titers were negative. Skin biopsies from the back and right abdomen revealed severe lichenoid interface dermatitis (IFD) with numerous dyskeratotic cells mimicking EM and eosinophils; however, direct immunofluorescence of the abdomen biopsy revealed an apparent suprabasal acantholysis with intercellular C3 in the lower half of the epidermis. Histologically, PNP was favored, but indirect immunofluorescence with monkey esophagus IgG was negative.

The skin lesions progressed, and an additional skin biopsy from the left arm performed 1 month later revealed similar histologic features with intercellular IgG and C3 in the lower half of the epidermis with weak basement membrane C3 (Figure 1). Serology also confirmed elevated serum antidesmoglein 1 and 3 antibodies. Thus, in the clinical setting of an erosive mucositis with EM-like and pemphigoidlike eruptions associated with B-cell lymphoma, the patient was diagnosed with PNP.

Although antidesmoglein 3 antibody was shown to be a pathologic driver in PNP, there is a weak correlation between antibody profiles and clinical presentation.⁸ In one case of PNP, antidesmoglein 3 antibody was negative, suggesting that lichenoid IFD may cause the phenotypic findings in PNP.⁹ Thus, the development of nail scarring in PNP may be explained by the presence of lichenoid IFD that is characteristic of PNP. However, the variation in antibody profile in PNP likely is a consequence of epitope spreading.

To the Editor:

Lichen sclerosus is a chronic inflammatory skin disease of unknown cause that predominantly affects the anogenital region, but isolated extragenital lesions occur in 6% to 15% of patients. The buttocks, thighs, neck, shoulder, upper torso, and wrists most commonly are involved; the face rarely is affected.^1,2 Although the etiology of lichen sclerosus remains undetermined, there is growing evidence that autoimmunity may play a role.¹ Lichen sclerosus more commonly is seen in women, and the disease can present at any age, with a bimodal onset in prepubertal children and in postmenopausal women and men in the fourth decade of life.^1-3 A PubMed search of articles indexed for MEDLINE using the terms lichen and eyelid and manually screened revealed 6 cases of lichen sclerosus involving the eyelid.^2-4 We describe a case of lichen sclerosus involving the eyelid and its histopathology.

A 45-year-old woman was referred to dermatology for evaluation of a right lower eyelid lesion of 3 months’ duration. She first noted a small white patch under the eyelid that had doubled in size and felt firm without bleeding or ulceration. Her medical history was unremarkable, and there was no history of ophthalmic conditions, autoimmune disease, trauma, or cancer. An ophthalmic examination was normal, except for a 20×8-mm, flat, depigmented, firm papule with scalloped borders involving the right lower eyelid margin and extending inferiorly without evidence of madarosis or ulceration (Figure 1). She underwent an incisional biopsy that revealed the diagnosis of lichen sclerosus et atrophicus (Figure 2). A full dermatologic evaluation included a genital examination and did not reveal any additional lesions. Tacrolimus ointment was started to avoid the need for long-term use of periocular steroids and their complications.

Histopathology is useful to distinguish among these entities. Although there are no specific features separating lichen sclerosus from a morphea overlap and both entities often are classified by clinical presentation, lichen sclerosus demonstrates epidermal atrophy, follicular plugging, homogenized collagen in the upper dermis with dermal edema, and lichenoid lymphocytic infiltrate (Figure 2).¹ Extragenital lesions in particular also have been noted to have more epidermal atrophy and decreased rete ridges.²

To the Editor:

Lichen sclerosus is a chronic inflammatory skin disease of unknown cause that predominantly affects the anogenital region, but isolated extragenital lesions occur in 6% to 15% of patients. The buttocks, thighs, neck, shoulder, upper torso, and wrists most commonly are involved; the face rarely is affected.^1,2 Although the etiology of lichen sclerosus remains undetermined, there is growing evidence that autoimmunity may play a role.¹ Lichen sclerosus more commonly is seen in women, and the disease can present at any age, with a bimodal onset in prepubertal children and in postmenopausal women and men in the fourth decade of life.^1-3 A PubMed search of articles indexed for MEDLINE using the terms lichen and eyelid and manually screened revealed 6 cases of lichen sclerosus involving the eyelid.^2-4 We describe a case of lichen sclerosus involving the eyelid and its histopathology.

A 45-year-old woman was referred to dermatology for evaluation of a right lower eyelid lesion of 3 months’ duration. She first noted a small white patch under the eyelid that had doubled in size and felt firm without bleeding or ulceration. Her medical history was unremarkable, and there was no history of ophthalmic conditions, autoimmune disease, trauma, or cancer. An ophthalmic examination was normal, except for a 20×8-mm, flat, depigmented, firm papule with scalloped borders involving the right lower eyelid margin and extending inferiorly without evidence of madarosis or ulceration (Figure 1). She underwent an incisional biopsy that revealed the diagnosis of lichen sclerosus et atrophicus (Figure 2). A full dermatologic evaluation included a genital examination and did not reveal any additional lesions. Tacrolimus ointment was started to avoid the need for long-term use of periocular steroids and their complications.

Histopathology is useful to distinguish among these entities. Although there are no specific features separating lichen sclerosus from a morphea overlap and both entities often are classified by clinical presentation, lichen sclerosus demonstrates epidermal atrophy, follicular plugging, homogenized collagen in the upper dermis with dermal edema, and lichenoid lymphocytic infiltrate (Figure 2).¹ Extragenital lesions in particular also have been noted to have more epidermal atrophy and decreased rete ridges.²

To the Editor:

Lichen sclerosus is a chronic inflammatory skin disease of unknown cause that predominantly affects the anogenital region, but isolated extragenital lesions occur in 6% to 15% of patients. The buttocks, thighs, neck, shoulder, upper torso, and wrists most commonly are involved; the face rarely is affected.^1,2 Although the etiology of lichen sclerosus remains undetermined, there is growing evidence that autoimmunity may play a role.¹ Lichen sclerosus more commonly is seen in women, and the disease can present at any age, with a bimodal onset in prepubertal children and in postmenopausal women and men in the fourth decade of life.^1-3 A PubMed search of articles indexed for MEDLINE using the terms lichen and eyelid and manually screened revealed 6 cases of lichen sclerosus involving the eyelid.^2-4 We describe a case of lichen sclerosus involving the eyelid and its histopathology.

A 45-year-old woman was referred to dermatology for evaluation of a right lower eyelid lesion of 3 months’ duration. She first noted a small white patch under the eyelid that had doubled in size and felt firm without bleeding or ulceration. Her medical history was unremarkable, and there was no history of ophthalmic conditions, autoimmune disease, trauma, or cancer. An ophthalmic examination was normal, except for a 20×8-mm, flat, depigmented, firm papule with scalloped borders involving the right lower eyelid margin and extending inferiorly without evidence of madarosis or ulceration (Figure 1). She underwent an incisional biopsy that revealed the diagnosis of lichen sclerosus et atrophicus (Figure 2). A full dermatologic evaluation included a genital examination and did not reveal any additional lesions. Tacrolimus ointment was started to avoid the need for long-term use of periocular steroids and their complications.

Histopathology is useful to distinguish among these entities. Although there are no specific features separating lichen sclerosus from a morphea overlap and both entities often are classified by clinical presentation, lichen sclerosus demonstrates epidermal atrophy, follicular plugging, homogenized collagen in the upper dermis with dermal edema, and lichenoid lymphocytic infiltrate (Figure 2).¹ Extragenital lesions in particular also have been noted to have more epidermal atrophy and decreased rete ridges.²