Clinical Psychiatry News

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

Two themes have emerged recently in my psychotherapy practice, and in the mirror: relief and exhaustion. Some peace in the public discourse, or at least a pause in the ominous discord, has had the effect of a lightening, an unburdening. Some release from a contracted sense of tension around the specifics of violence and a broader sense of civil fracture has been palpable like a big, deep breath, exhaled. No sensible person would mistake this for being out of the metaphoric woods. A virus menaces and mutates, economic woes follow, and lots of us don’t get along. But, yes, there is some relief, some good change.

But even good change, even a downshift into relief, can pose some challenges to look for and overcome.

Consider for a moment the notion that every change represents a loss, a metaphoric “death” of the prior state of things. This is true of big, painful losses, like the death of a loved one, and small ones, like finding an empty cookie jar. It’s also true in changes we associate with benefit or relief: a refund check, a job promotion, a resolving migraine, or the breaking out of some civility.

In changes of all sorts, the world outside of one’s mind has shifted – at odds, momentarily, with our inner, now obsolete understanding of that changed world. The inside of the head does not match the outside. How we make that adjustment, so “inside = outside,” is a clinically familiar process: it’s grieving, with a sequence famously elaborated upon by Elisabeth Kübler-Ross, MD,¹ and others.

We all likely know the steps: shock/denial, anger, “bargaining,” depression, and acceptance. A quick review: Our initial anxious/threat reaction leads to grievous judgment, to rationalizing “woulda/coulda/shoulda’s,” then to truly landing in the disappointment of a loss or change, and the accepting of a new steady state. Inside proceeds to match outside.

So, what then of relief? How do we process “good” change? I think we still must move from “in ≠ out” to “in = out,” navigating some pitfalls along the way.

Initial threat often remains; apprehension of the “new” still can generate energy, and even a sense of threat, regardless of a kiss or a shove. Our brainstems run roughshod over this first phase.

Step two is about judgment. We can move past the threat to, “How do I feel about it?” Here’s where grievous feeling gets swapped out for something more peak-positive – joy, or relief if the change represents an ending of a state of suffering, tension, or uncertainty.

The “bargaining” step still happens, but often around a kind of testing regimen: Is this too good to be true? Is it really different? We run scenarios.

The thud of disappointment also gets a makeover. It’s a settling into the beneficial change and its associations: gratitude, a sense of energy shifting.

The bookend “OK” seems anodyne here – why would anyone not accept relief, some good change?² But it can nevertheless represent a challenge for many. The receding tension of the last year could open into a burst of energy, but I’m finding that exhaustion is just as or more common. That’s not illness, but a weary exhaling from the longest of held breaths.

One other twist: What happens when one of those steps is an individual obstacle, trigger, or hard-to-hold state? Especially for those with deep experience in disappointment or even trauma, buying into acceptance of a new normal can feel like a fool’s game. This is an especially complex spot for individuals who won’t quite allow for joyful acceptance to break out, lest it reveals itself as a humiliating trick or a too-brief respite from the “usual.”

Mindfulness practices, such as meditation, are helpful in managing this process. Committed time and optimal conditions to witness and adapt to the various inner states that ebb and flow generate a clear therapeutic benefit. Incorporating meditation training into my work with psychotherapy patients also becomes a kind of diagnostic force multiplier. Patients improve their identification of somatic manifestations, emotional reactions, and cycling ruminations of thought. What generates distraction and loss of mindful attention becomes better recognized. Contemplative work in between sessions becomes more productive.

What else do I advise?³ Patience, and some compassion for ourselves in this unusual time. Grief, and relief, are complex but truly human processes that generate not just one state of experience, but a cascade of them. While that cascade can hurt, it’s actually normal, not illness. But it can be exhausting.
 

Dr. Sazima is a Northern California psychiatrist, educator, and author. He is senior behavioral faculty at the Stanford-O’Connor Family Medicine Residency Program in San José, Calif. His latest book is “Practical Mindfulness: A Physician’s No-Nonsense Guide to Meditation for Beginners,” Miami: Mango Publishing, 2021. Dr. Sazima disclosed no relevant financial relationships.

References

1. Kübler-Ross E. “On Death And Dying,” New York: Simon & Schuster, 1969.

2. Selye H. “Stress Without Distress,” New York: Lippincott, Williams & Wilkins, 1974.

3. Sazima G. “Practical Mindfulness: A Physician’s No-Nonsense Guide to Meditation for Beginners,” Miami: Mango Publishing, 2021.

Two themes have emerged recently in my psychotherapy practice, and in the mirror: relief and exhaustion. Some peace in the public discourse, or at least a pause in the ominous discord, has had the effect of a lightening, an unburdening. Some release from a contracted sense of tension around the specifics of violence and a broader sense of civil fracture has been palpable like a big, deep breath, exhaled. No sensible person would mistake this for being out of the metaphoric woods. A virus menaces and mutates, economic woes follow, and lots of us don’t get along. But, yes, there is some relief, some good change.

But even good change, even a downshift into relief, can pose some challenges to look for and overcome.

Consider for a moment the notion that every change represents a loss, a metaphoric “death” of the prior state of things. This is true of big, painful losses, like the death of a loved one, and small ones, like finding an empty cookie jar. It’s also true in changes we associate with benefit or relief: a refund check, a job promotion, a resolving migraine, or the breaking out of some civility.

In changes of all sorts, the world outside of one’s mind has shifted – at odds, momentarily, with our inner, now obsolete understanding of that changed world. The inside of the head does not match the outside. How we make that adjustment, so “inside = outside,” is a clinically familiar process: it’s grieving, with a sequence famously elaborated upon by Elisabeth Kübler-Ross, MD,¹ and others.

We all likely know the steps: shock/denial, anger, “bargaining,” depression, and acceptance. A quick review: Our initial anxious/threat reaction leads to grievous judgment, to rationalizing “woulda/coulda/shoulda’s,” then to truly landing in the disappointment of a loss or change, and the accepting of a new steady state. Inside proceeds to match outside.

So, what then of relief? How do we process “good” change? I think we still must move from “in ≠ out” to “in = out,” navigating some pitfalls along the way.

Initial threat often remains; apprehension of the “new” still can generate energy, and even a sense of threat, regardless of a kiss or a shove. Our brainstems run roughshod over this first phase.

Step two is about judgment. We can move past the threat to, “How do I feel about it?” Here’s where grievous feeling gets swapped out for something more peak-positive – joy, or relief if the change represents an ending of a state of suffering, tension, or uncertainty.

The “bargaining” step still happens, but often around a kind of testing regimen: Is this too good to be true? Is it really different? We run scenarios.

The thud of disappointment also gets a makeover. It’s a settling into the beneficial change and its associations: gratitude, a sense of energy shifting.

The bookend “OK” seems anodyne here – why would anyone not accept relief, some good change?² But it can nevertheless represent a challenge for many. The receding tension of the last year could open into a burst of energy, but I’m finding that exhaustion is just as or more common. That’s not illness, but a weary exhaling from the longest of held breaths.

One other twist: What happens when one of those steps is an individual obstacle, trigger, or hard-to-hold state? Especially for those with deep experience in disappointment or even trauma, buying into acceptance of a new normal can feel like a fool’s game. This is an especially complex spot for individuals who won’t quite allow for joyful acceptance to break out, lest it reveals itself as a humiliating trick or a too-brief respite from the “usual.”

Mindfulness practices, such as meditation, are helpful in managing this process. Committed time and optimal conditions to witness and adapt to the various inner states that ebb and flow generate a clear therapeutic benefit. Incorporating meditation training into my work with psychotherapy patients also becomes a kind of diagnostic force multiplier. Patients improve their identification of somatic manifestations, emotional reactions, and cycling ruminations of thought. What generates distraction and loss of mindful attention becomes better recognized. Contemplative work in between sessions becomes more productive.

What else do I advise?³ Patience, and some compassion for ourselves in this unusual time. Grief, and relief, are complex but truly human processes that generate not just one state of experience, but a cascade of them. While that cascade can hurt, it’s actually normal, not illness. But it can be exhausting.
 

Dr. Sazima is a Northern California psychiatrist, educator, and author. He is senior behavioral faculty at the Stanford-O’Connor Family Medicine Residency Program in San José, Calif. His latest book is “Practical Mindfulness: A Physician’s No-Nonsense Guide to Meditation for Beginners,” Miami: Mango Publishing, 2021. Dr. Sazima disclosed no relevant financial relationships.

References

1. Kübler-Ross E. “On Death And Dying,” New York: Simon & Schuster, 1969.

2. Selye H. “Stress Without Distress,” New York: Lippincott, Williams & Wilkins, 1974.

3. Sazima G. “Practical Mindfulness: A Physician’s No-Nonsense Guide to Meditation for Beginners,” Miami: Mango Publishing, 2021.

Two themes have emerged recently in my psychotherapy practice, and in the mirror: relief and exhaustion. Some peace in the public discourse, or at least a pause in the ominous discord, has had the effect of a lightening, an unburdening. Some release from a contracted sense of tension around the specifics of violence and a broader sense of civil fracture has been palpable like a big, deep breath, exhaled. No sensible person would mistake this for being out of the metaphoric woods. A virus menaces and mutates, economic woes follow, and lots of us don’t get along. But, yes, there is some relief, some good change.

But even good change, even a downshift into relief, can pose some challenges to look for and overcome.

Consider for a moment the notion that every change represents a loss, a metaphoric “death” of the prior state of things. This is true of big, painful losses, like the death of a loved one, and small ones, like finding an empty cookie jar. It’s also true in changes we associate with benefit or relief: a refund check, a job promotion, a resolving migraine, or the breaking out of some civility.

In changes of all sorts, the world outside of one’s mind has shifted – at odds, momentarily, with our inner, now obsolete understanding of that changed world. The inside of the head does not match the outside. How we make that adjustment, so “inside = outside,” is a clinically familiar process: it’s grieving, with a sequence famously elaborated upon by Elisabeth Kübler-Ross, MD,¹ and others.

We all likely know the steps: shock/denial, anger, “bargaining,” depression, and acceptance. A quick review: Our initial anxious/threat reaction leads to grievous judgment, to rationalizing “woulda/coulda/shoulda’s,” then to truly landing in the disappointment of a loss or change, and the accepting of a new steady state. Inside proceeds to match outside.

So, what then of relief? How do we process “good” change? I think we still must move from “in ≠ out” to “in = out,” navigating some pitfalls along the way.

Initial threat often remains; apprehension of the “new” still can generate energy, and even a sense of threat, regardless of a kiss or a shove. Our brainstems run roughshod over this first phase.

Step two is about judgment. We can move past the threat to, “How do I feel about it?” Here’s where grievous feeling gets swapped out for something more peak-positive – joy, or relief if the change represents an ending of a state of suffering, tension, or uncertainty.

The “bargaining” step still happens, but often around a kind of testing regimen: Is this too good to be true? Is it really different? We run scenarios.

The thud of disappointment also gets a makeover. It’s a settling into the beneficial change and its associations: gratitude, a sense of energy shifting.

The bookend “OK” seems anodyne here – why would anyone not accept relief, some good change?² But it can nevertheless represent a challenge for many. The receding tension of the last year could open into a burst of energy, but I’m finding that exhaustion is just as or more common. That’s not illness, but a weary exhaling from the longest of held breaths.

One other twist: What happens when one of those steps is an individual obstacle, trigger, or hard-to-hold state? Especially for those with deep experience in disappointment or even trauma, buying into acceptance of a new normal can feel like a fool’s game. This is an especially complex spot for individuals who won’t quite allow for joyful acceptance to break out, lest it reveals itself as a humiliating trick or a too-brief respite from the “usual.”

Mindfulness practices, such as meditation, are helpful in managing this process. Committed time and optimal conditions to witness and adapt to the various inner states that ebb and flow generate a clear therapeutic benefit. Incorporating meditation training into my work with psychotherapy patients also becomes a kind of diagnostic force multiplier. Patients improve their identification of somatic manifestations, emotional reactions, and cycling ruminations of thought. What generates distraction and loss of mindful attention becomes better recognized. Contemplative work in between sessions becomes more productive.

What else do I advise?³ Patience, and some compassion for ourselves in this unusual time. Grief, and relief, are complex but truly human processes that generate not just one state of experience, but a cascade of them. While that cascade can hurt, it’s actually normal, not illness. But it can be exhausting.
 

Dr. Sazima is a Northern California psychiatrist, educator, and author. He is senior behavioral faculty at the Stanford-O’Connor Family Medicine Residency Program in San José, Calif. His latest book is “Practical Mindfulness: A Physician’s No-Nonsense Guide to Meditation for Beginners,” Miami: Mango Publishing, 2021. Dr. Sazima disclosed no relevant financial relationships.

References

1. Kübler-Ross E. “On Death And Dying,” New York: Simon & Schuster, 1969.

2. Selye H. “Stress Without Distress,” New York: Lippincott, Williams & Wilkins, 1974.

3. Sazima G. “Practical Mindfulness: A Physician’s No-Nonsense Guide to Meditation for Beginners,” Miami: Mango Publishing, 2021.

A medical journal is retracting a paper after a psychiatrist alleged that the managing editor closely copied and published her withdrawn work and claimed it for his own.

In addition, the managing editor, Gary VandenBos, PhD, has resigned at the journal’s request, according to an email sent to the paper’s original author, psychiatrist Amy Barnhorst, MD, vice chair for community mental health at the University of California, Davis, and coauthor and UC Davis colleague Rocco Pallin, MPH.

Dr. Barnhorst shared emails – from the journal’s publisher, Springer Publishing Company, and from the editor in chief, Morgan Sammons, PhD – with this news organization.

The retraction is the end of a saga that began when Dr. Barnhorst and Dr. Pallin submitted a paper, at Dr. VandenBos’s request, to the Journal of Health Service Psychology, published by Springer.

As previously reported by this news organization, Dr. Barnhorst and Dr. Pallin eventually decided to withdraw the paper and were later notified by Dr. VandenBos that he’d published a similar article under his own authorship. Michael O. Miller, a retired judge who trained as a psychologist, was listed as a coauthor.

Dr. VandenBos did not acknowledge how heavily his paper borrowed from the withdrawn article by Dr. Barnhorst and Dr. Pallin The two women – acknowledged experts in the article’s subject matter on how physicians can talk to patients about gun violence – immediately notified Dr. Sammons and Springer Publishing when they saw the published piece, saying they believed it plagiarized their original submission.

According to the e-mail Springer sent to Dr. Barnhorst, the publisher investigated and said that it would “be retracting the article shortly.”

The retraction notice will state: “The Editor in Chief and the authors, Dr. VandenBos and Mr. Miller, have retracted this article, as it significantly overlaps with an unpublished manuscript by Amy Barnhorst and Rocco Pallin.” It also states that “[Dr.] VandenBos accepts full responsibility for the overlap.”

The original article will still be available, but it will be marked as “retracted” and feature a link to the retraction notice.

Dr. Barnhorst, who garnered at least 40,000 likes when she tweeted about the alleged theft of her work, said in an interview that she and Dr. Pallin are “glad to see that the investigation is complete and the retraction has been issued.”

“At least we can now submit it to a new journal in a version that appropriately represents our work and expertise,” said Dr. Barnhorst. “I still have no idea how or why this happened, nor how much of it was intentional and on whose part, but I guess I never will!”

Editor removed

When contacted by this news organization to comment on the retraction and removal of Dr. VandenBos as managing editor, Dr. Sammons said it was not possible because, “I treat such correspondence as confidential.”

Dr. Sammons said he could “confirm that our investigation is reaching its conclusion and my colleagues at Springer Nature would be happy to contact you when we can provide a further update.”

Springer spokesperson Anne Korn also would not comment beyond saying, “The conclusion of our investigation is still in progress and may take a little additional time.”  

In the letter sent to Dr. Barnhorst and Dr. Pallin, Dr. Sammons said he had “asked for and accepted the resignation of Dr. VandenBos,” and that the resignation will be announced “in the upcoming print issue of our journal.”

Dr. Sammons said he also notified the dean of the University of Arizona College of Law that Mr. Miller, who held a position at the school, was not aware of the original submission by the two women. Even so, the school suspended Mr. Miller’s academic appointment, according to Dr. Sammons’ letter.

The editor in chief also said that, while “[Dr.] VandenBos’ errors were substantial and had substantial consequences, my investigation did not find any intent to plagiarize your work.”

He apologized again to Dr. Barnhorst and Dr. Pallin, though, adding, “I and my associate editors have initiated a revision of our publications processes to ensure that errors such as the above do not occur in the future, and I apologize again that this lapse affected you and your scholarly work.”

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

A medical journal is retracting a paper after a psychiatrist alleged that the managing editor closely copied and published her withdrawn work and claimed it for his own.

In addition, the managing editor, Gary VandenBos, PhD, has resigned at the journal’s request, according to an email sent to the paper’s original author, psychiatrist Amy Barnhorst, MD, vice chair for community mental health at the University of California, Davis, and coauthor and UC Davis colleague Rocco Pallin, MPH.

Dr. Barnhorst shared emails – from the journal’s publisher, Springer Publishing Company, and from the editor in chief, Morgan Sammons, PhD – with this news organization.

The retraction is the end of a saga that began when Dr. Barnhorst and Dr. Pallin submitted a paper, at Dr. VandenBos’s request, to the Journal of Health Service Psychology, published by Springer.

As previously reported by this news organization, Dr. Barnhorst and Dr. Pallin eventually decided to withdraw the paper and were later notified by Dr. VandenBos that he’d published a similar article under his own authorship. Michael O. Miller, a retired judge who trained as a psychologist, was listed as a coauthor.

Dr. VandenBos did not acknowledge how heavily his paper borrowed from the withdrawn article by Dr. Barnhorst and Dr. Pallin The two women – acknowledged experts in the article’s subject matter on how physicians can talk to patients about gun violence – immediately notified Dr. Sammons and Springer Publishing when they saw the published piece, saying they believed it plagiarized their original submission.

According to the e-mail Springer sent to Dr. Barnhorst, the publisher investigated and said that it would “be retracting the article shortly.”

The retraction notice will state: “The Editor in Chief and the authors, Dr. VandenBos and Mr. Miller, have retracted this article, as it significantly overlaps with an unpublished manuscript by Amy Barnhorst and Rocco Pallin.” It also states that “[Dr.] VandenBos accepts full responsibility for the overlap.”

The original article will still be available, but it will be marked as “retracted” and feature a link to the retraction notice.

Dr. Barnhorst, who garnered at least 40,000 likes when she tweeted about the alleged theft of her work, said in an interview that she and Dr. Pallin are “glad to see that the investigation is complete and the retraction has been issued.”

“At least we can now submit it to a new journal in a version that appropriately represents our work and expertise,” said Dr. Barnhorst. “I still have no idea how or why this happened, nor how much of it was intentional and on whose part, but I guess I never will!”

Editor removed

When contacted by this news organization to comment on the retraction and removal of Dr. VandenBos as managing editor, Dr. Sammons said it was not possible because, “I treat such correspondence as confidential.”

Dr. Sammons said he could “confirm that our investigation is reaching its conclusion and my colleagues at Springer Nature would be happy to contact you when we can provide a further update.”

Springer spokesperson Anne Korn also would not comment beyond saying, “The conclusion of our investigation is still in progress and may take a little additional time.”  

In the letter sent to Dr. Barnhorst and Dr. Pallin, Dr. Sammons said he had “asked for and accepted the resignation of Dr. VandenBos,” and that the resignation will be announced “in the upcoming print issue of our journal.”

Dr. Sammons said he also notified the dean of the University of Arizona College of Law that Mr. Miller, who held a position at the school, was not aware of the original submission by the two women. Even so, the school suspended Mr. Miller’s academic appointment, according to Dr. Sammons’ letter.

The editor in chief also said that, while “[Dr.] VandenBos’ errors were substantial and had substantial consequences, my investigation did not find any intent to plagiarize your work.”

He apologized again to Dr. Barnhorst and Dr. Pallin, though, adding, “I and my associate editors have initiated a revision of our publications processes to ensure that errors such as the above do not occur in the future, and I apologize again that this lapse affected you and your scholarly work.”

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

A medical journal is retracting a paper after a psychiatrist alleged that the managing editor closely copied and published her withdrawn work and claimed it for his own.

In addition, the managing editor, Gary VandenBos, PhD, has resigned at the journal’s request, according to an email sent to the paper’s original author, psychiatrist Amy Barnhorst, MD, vice chair for community mental health at the University of California, Davis, and coauthor and UC Davis colleague Rocco Pallin, MPH.

Dr. Barnhorst shared emails – from the journal’s publisher, Springer Publishing Company, and from the editor in chief, Morgan Sammons, PhD – with this news organization.

The retraction is the end of a saga that began when Dr. Barnhorst and Dr. Pallin submitted a paper, at Dr. VandenBos’s request, to the Journal of Health Service Psychology, published by Springer.

As previously reported by this news organization, Dr. Barnhorst and Dr. Pallin eventually decided to withdraw the paper and were later notified by Dr. VandenBos that he’d published a similar article under his own authorship. Michael O. Miller, a retired judge who trained as a psychologist, was listed as a coauthor.

Dr. VandenBos did not acknowledge how heavily his paper borrowed from the withdrawn article by Dr. Barnhorst and Dr. Pallin The two women – acknowledged experts in the article’s subject matter on how physicians can talk to patients about gun violence – immediately notified Dr. Sammons and Springer Publishing when they saw the published piece, saying they believed it plagiarized their original submission.

According to the e-mail Springer sent to Dr. Barnhorst, the publisher investigated and said that it would “be retracting the article shortly.”

The retraction notice will state: “The Editor in Chief and the authors, Dr. VandenBos and Mr. Miller, have retracted this article, as it significantly overlaps with an unpublished manuscript by Amy Barnhorst and Rocco Pallin.” It also states that “[Dr.] VandenBos accepts full responsibility for the overlap.”

The original article will still be available, but it will be marked as “retracted” and feature a link to the retraction notice.

Dr. Barnhorst, who garnered at least 40,000 likes when she tweeted about the alleged theft of her work, said in an interview that she and Dr. Pallin are “glad to see that the investigation is complete and the retraction has been issued.”

“At least we can now submit it to a new journal in a version that appropriately represents our work and expertise,” said Dr. Barnhorst. “I still have no idea how or why this happened, nor how much of it was intentional and on whose part, but I guess I never will!”

Editor removed

When contacted by this news organization to comment on the retraction and removal of Dr. VandenBos as managing editor, Dr. Sammons said it was not possible because, “I treat such correspondence as confidential.”

Dr. Sammons said he could “confirm that our investigation is reaching its conclusion and my colleagues at Springer Nature would be happy to contact you when we can provide a further update.”

Springer spokesperson Anne Korn also would not comment beyond saying, “The conclusion of our investigation is still in progress and may take a little additional time.”  

In the letter sent to Dr. Barnhorst and Dr. Pallin, Dr. Sammons said he had “asked for and accepted the resignation of Dr. VandenBos,” and that the resignation will be announced “in the upcoming print issue of our journal.”

Dr. Sammons said he also notified the dean of the University of Arizona College of Law that Mr. Miller, who held a position at the school, was not aware of the original submission by the two women. Even so, the school suspended Mr. Miller’s academic appointment, according to Dr. Sammons’ letter.

The editor in chief also said that, while “[Dr.] VandenBos’ errors were substantial and had substantial consequences, my investigation did not find any intent to plagiarize your work.”

He apologized again to Dr. Barnhorst and Dr. Pallin, though, adding, “I and my associate editors have initiated a revision of our publications processes to ensure that errors such as the above do not occur in the future, and I apologize again that this lapse affected you and your scholarly work.”

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

Posttraumatic stress disorder may occur in up to a third of patients who recover from severe COVID-19 infection, new research suggests.

A study of more than 300 patients who presented to the emergency department with the virus showed a 30.2% prevalence for PTSD 30-120 days after COVID recovery.

Factors linked to higher rates of PTSD included experiencing delirium or agitation during the acute COVID phase or having persistent medical symptoms after hospitalization. 

Additional diagnoses, such as depressive and hypomanic episodes and generalized anxiety disorder (GAD), were also present in some of the survivors.

“Previous coronavirus epidemics were associated with PTSD diagnoses in postillness stages, with meta-analytic findings indicating a prevalence of 32.2%,” write the investigators, led by Delfina Janiri, MD, department of psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.

However, data focused specifically on COVID-19 have been “piecemeal,” they add.

The findings were published online Feb. 18 in a research letter in JAMA Psychiatry.
 

A traumatic event

From April to October 2020, the researchers assessed 381 consecutive patients (100% white; 56.4% men; mean age, 55.3 years) who presented to the ED and subsequently participated in a health check at the Fondazione Policlinico Universitario Agostino Gemelli.

The mean length of stay for the 309 patients hospitalized with severe COVID-19 was 18.4 days.

Results showed that 115 participants (30.2%) had PTSD, based on DSM-5 criteria, and 55.7% of the women had the disorder. Additional diagnoses found in the full patient population included:

• Depressive episodes (17.3%).
• GAD (7%).
• Hypomanic episodes (0.7%).
• Psychotic disorders (0.2%).

Patients with PTSD had higher rates than those without PTSD of a previous history of psychiatric disorders (34.8% vs. 20.7%; P = .003) and of delirium or agitation during hospitalization, as assessed with the Confusion Assessment Method (16.5% vs. 6.4%; P = .002).

In addition, 62.6% of those with PTSD had three or more persistent COVID-19 symptoms vs. 37.2% of their counterparts without PTSD (P < .001).

After logistic regression analyses, significant factors associated with a PTSD diagnosis were persistent medical symptoms (P = .002), delirium or agitation (P = .02), and being female (P = .02).

The investigators note that their results are “in line” with findings reported in research examining other traumatic events. This includes about 30% of Hurricane Katrina survivors who experienced PTSD, as did around 25% of survivors of the 2011 “Great Japan Earthquake and Tsunami.”

Study limitations cited include the “relatively small” size of the patient population, that it focused on only one participating center, and that it didn’t include a control group of non-COVID patients who reported to the ED.

“Further longitudinal studies are needed to tailor therapeutic interventions and prevention strategies,” the researchers write.

Dr. Janiri and four of the five other authors have disclosed no relevant financial relationships. The other author, Gabriele Sani, MD, reported having received personal fees from Angelini Spa, Janssen, and Lundbeck outside the submitted work.

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

Posttraumatic stress disorder may occur in up to a third of patients who recover from severe COVID-19 infection, new research suggests.

A study of more than 300 patients who presented to the emergency department with the virus showed a 30.2% prevalence for PTSD 30-120 days after COVID recovery.

Factors linked to higher rates of PTSD included experiencing delirium or agitation during the acute COVID phase or having persistent medical symptoms after hospitalization. 

Additional diagnoses, such as depressive and hypomanic episodes and generalized anxiety disorder (GAD), were also present in some of the survivors.

“Previous coronavirus epidemics were associated with PTSD diagnoses in postillness stages, with meta-analytic findings indicating a prevalence of 32.2%,” write the investigators, led by Delfina Janiri, MD, department of psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.

However, data focused specifically on COVID-19 have been “piecemeal,” they add.

The findings were published online Feb. 18 in a research letter in JAMA Psychiatry.
 

A traumatic event

From April to October 2020, the researchers assessed 381 consecutive patients (100% white; 56.4% men; mean age, 55.3 years) who presented to the ED and subsequently participated in a health check at the Fondazione Policlinico Universitario Agostino Gemelli.

The mean length of stay for the 309 patients hospitalized with severe COVID-19 was 18.4 days.

Results showed that 115 participants (30.2%) had PTSD, based on DSM-5 criteria, and 55.7% of the women had the disorder. Additional diagnoses found in the full patient population included:

• Depressive episodes (17.3%).
• GAD (7%).
• Hypomanic episodes (0.7%).
• Psychotic disorders (0.2%).

Patients with PTSD had higher rates than those without PTSD of a previous history of psychiatric disorders (34.8% vs. 20.7%; P = .003) and of delirium or agitation during hospitalization, as assessed with the Confusion Assessment Method (16.5% vs. 6.4%; P = .002).

In addition, 62.6% of those with PTSD had three or more persistent COVID-19 symptoms vs. 37.2% of their counterparts without PTSD (P < .001).

After logistic regression analyses, significant factors associated with a PTSD diagnosis were persistent medical symptoms (P = .002), delirium or agitation (P = .02), and being female (P = .02).

The investigators note that their results are “in line” with findings reported in research examining other traumatic events. This includes about 30% of Hurricane Katrina survivors who experienced PTSD, as did around 25% of survivors of the 2011 “Great Japan Earthquake and Tsunami.”

Study limitations cited include the “relatively small” size of the patient population, that it focused on only one participating center, and that it didn’t include a control group of non-COVID patients who reported to the ED.

“Further longitudinal studies are needed to tailor therapeutic interventions and prevention strategies,” the researchers write.

Dr. Janiri and four of the five other authors have disclosed no relevant financial relationships. The other author, Gabriele Sani, MD, reported having received personal fees from Angelini Spa, Janssen, and Lundbeck outside the submitted work.

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

Posttraumatic stress disorder may occur in up to a third of patients who recover from severe COVID-19 infection, new research suggests.

A study of more than 300 patients who presented to the emergency department with the virus showed a 30.2% prevalence for PTSD 30-120 days after COVID recovery.

Factors linked to higher rates of PTSD included experiencing delirium or agitation during the acute COVID phase or having persistent medical symptoms after hospitalization. 

Additional diagnoses, such as depressive and hypomanic episodes and generalized anxiety disorder (GAD), were also present in some of the survivors.

“Previous coronavirus epidemics were associated with PTSD diagnoses in postillness stages, with meta-analytic findings indicating a prevalence of 32.2%,” write the investigators, led by Delfina Janiri, MD, department of psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.

However, data focused specifically on COVID-19 have been “piecemeal,” they add.

The findings were published online Feb. 18 in a research letter in JAMA Psychiatry.
 

A traumatic event

From April to October 2020, the researchers assessed 381 consecutive patients (100% white; 56.4% men; mean age, 55.3 years) who presented to the ED and subsequently participated in a health check at the Fondazione Policlinico Universitario Agostino Gemelli.

The mean length of stay for the 309 patients hospitalized with severe COVID-19 was 18.4 days.

Results showed that 115 participants (30.2%) had PTSD, based on DSM-5 criteria, and 55.7% of the women had the disorder. Additional diagnoses found in the full patient population included:

• Depressive episodes (17.3%).
• GAD (7%).
• Hypomanic episodes (0.7%).
• Psychotic disorders (0.2%).

Patients with PTSD had higher rates than those without PTSD of a previous history of psychiatric disorders (34.8% vs. 20.7%; P = .003) and of delirium or agitation during hospitalization, as assessed with the Confusion Assessment Method (16.5% vs. 6.4%; P = .002).

In addition, 62.6% of those with PTSD had three or more persistent COVID-19 symptoms vs. 37.2% of their counterparts without PTSD (P < .001).

After logistic regression analyses, significant factors associated with a PTSD diagnosis were persistent medical symptoms (P = .002), delirium or agitation (P = .02), and being female (P = .02).

The investigators note that their results are “in line” with findings reported in research examining other traumatic events. This includes about 30% of Hurricane Katrina survivors who experienced PTSD, as did around 25% of survivors of the 2011 “Great Japan Earthquake and Tsunami.”

Study limitations cited include the “relatively small” size of the patient population, that it focused on only one participating center, and that it didn’t include a control group of non-COVID patients who reported to the ED.

“Further longitudinal studies are needed to tailor therapeutic interventions and prevention strategies,” the researchers write.

Dr. Janiri and four of the five other authors have disclosed no relevant financial relationships. The other author, Gabriele Sani, MD, reported having received personal fees from Angelini Spa, Janssen, and Lundbeck outside the submitted work.

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

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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

Increased white matter hyperintensities (WMH) are strongly associated with Alzheimer’s disease, but new research reveals they are also a “core feature” of frontotemporal dementia (FTD) in findings that may help physicians make this difficult diagnosis that affects adults in their prime.

“The assessment of WMH can aid differential diagnosis of bvFTD [behavioral-variant FTD] against other neurodegenerative conditions in the absence of vascular risk factors, especially when considering their spatial distribution,” said senior author Ramón Landin-Romero, PhD, Appenzeller Neuroscience Fellow, Frontotemporal Dementia Research Group, University of Sydney.

“Clinicians can ask for specific sequences in routine MRI scans to visually detect WMH,” said Dr. Landin-Romero, who is also a senior lecturer in the School of Psychology and Brain and Mind Center.

The study was published online Feb. 17 in Neurology.
 

Difficult diagnosis

“FTD is a collection of unrecognized young-onset (before age 65) dementia syndromes that affect people in their prime,” said Dr. Landin-Romero. He added that heterogeneity in progression trajectories and symptoms, which can include changes in behavior and personality, language impairments, and psychosis, make it a difficult disease to diagnose.

“As such, our research was motivated by the need of sensitive and specific biomarkers of FTD, which are urgently needed to aid diagnosis, prognosis, and treatment development,” he said.

Previous research has been limited; there have only been a “handful” of cohort and case studies and studies involving individuals with mutations in one FTD-causative gene.

FTD is genetically and pathologically complex, and there has been no clear correlation between genetic mutations/underlying pathology and clinical presentation, Dr. Landin-Romero said.

WMH are common in older individuals and are linked to increased risk for cognitive impairment and dementia. Traditionally, they have been associated with vascular risk factors, such as smoking and diabetes. “But the presentation of WMH in FTD and its associations with the severity of symptoms and brain atrophy across FTD symptoms remains to be established,” said Dr. Landin-Romero.
 

Higher disease severity

To explore the possible association, the researchers studied 129 patients with either bvFTD (n = 64; mean age, 64 years) or Alzheimer’s disease (n = 65; mean age, 64.66 years).

Neuropsychological assessments, medical and neurologic examinations, clinical interview, and structural brain MRI were conducted for all patients, who were compared with 66 age-, sex-, and education-matched healthy control persons (mean age, 64.69 years).

Some participants in the FTD, Alzheimer’s disease, and healthy control groups (n = 54, 44, and 26, respectively) also underwent genetic screening. Postmortem pathology findings were available for a small number of FTD and Alzheimer’s disease participants (n = 13 and 5, respectively).

The medical history included lifestyle and cardiovascular risk factors, as well as other health and neurologic conditions and medication history. Hypertension, hypercholesterolemia, diabetes, and smoking were used to assess vascular risk.

The FTD and Alzheimer’s disease groups did not differ with regard to disease duration (3.55 years; standard deviation, 1.75, and 3.24 years; SD, 1.59, respectively). However, disease severity was significantly higher among those with FTD than among those with Alzheimer’s disease, as measured by the FTD Rating Scale Rasch score (–0.52; SD, 1.28, vs. 0.78; SD, 1.55; P < .001).

Compared with healthy controls, patients in the FTD and Alzheimer’s disease groups scored significantly lower on the Addenbrooke’s Cognitive Examination–Revised (ACE-R) or ACE-III scale. Patients with Alzheimer’s disease showed “disproportionately larger deficits” in memory and visuospatial processing, compared with those with FTD, whereas those with FTD performed significantly worse than those with Alzheimer’s disease in the fluency subdomain.

A larger number of patients in the FTD group screened positive for genetic abnormalities than in the Alzheimer’s disease group; no participants in the healthy control group had genetic mutations.
 

Unexpected findings

Mean WMH volume was significantly higher in participants with FTD than in participants with Alzheimer’s disease and in healthy controls (mean, 0.76 mL, 0.40 mL, and 0.12 mL respectively). These larger volumes contributed to greater disease severity and cortical atrophy. Moreover, disease severity was “found to be a strong predictor of WMH volume in FTD,” the authors stated. Among patients with FTD, WMH volumes did not differ significantly with regard to genetic mutation status or presence of strong family history.

After controlling for age, vascular risk did not significantly predict WMH volume in the FTD group (P = .16); however, that did not hold true in the Alzheimer’s disease group.

Increased WMH were associated with anterior brain regions in FTD and with posterior brain regions in Alzheimer’s disease. In both disorders, higher WMH volume in the corpus callosum was associated with poorer cognitive performance in the domain of attention.

“The spatial distribution of WMH mirrored patterns of brain atrophy in FTD and Alzheimer’s disease, was partially independent of cortical degeneration, and was correlated with cognitive deficits,” said Dr. Landin-Romero.

The findings were not what he and his research colleagues expected. “We were expecting that the amounts of WMH would be similar in FTD and Alzheimer’s disease, but we actually found higher levels in participants with FTD,” he said. Additionally, he anticipated that patients with either FTD or Alzheimer’s disease who had more severe disease would have more WMH, but that finding only held true for people with FTD.

“In sum, our findings show that WMH are a core feature of FTD and Alzheimer’s disease that can contribute to cognitive problems, and not simply as a marker of vascular disease,” said Dr. Landin-Romero.
 

Major research contribution

Commenting on the study, Jordi Matias-Guiu, PhD, MD, of the department of neurology, Hospital Clinico, San Carlos, Spain, considers the study to be a “great contribution to the field.” Dr. Matias-Guiu, who was not involved with the study, said that WMH “do not necessarily mean vascular pathology, and atrophy may partially explain these abnormalities and should be taken into account in the interpretation of brain MRI.

“WMH are present in both Alzheimer’s disease and FTD and are relevant to cognitive deficits found in these disorders,” he added.

The study was funded by grants from the National Health and Medical Research Council of Australia, the Dementia Research Team, and the ARC Center of Excellence in Cognition and Its Disorders. Dr. Landin-Romero is supported by the Appenzeller Neuroscience Fellowship in Alzheimer’s Disease and the ARC Center of Excellence in Cognition and Its Disorders Memory Program. The other authors’ disclosures are listed on the original article. Dr. Matias-Guiu reports no relevant financial relationships.

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

Increased white matter hyperintensities (WMH) are strongly associated with Alzheimer’s disease, but new research reveals they are also a “core feature” of frontotemporal dementia (FTD) in findings that may help physicians make this difficult diagnosis that affects adults in their prime.

“The assessment of WMH can aid differential diagnosis of bvFTD [behavioral-variant FTD] against other neurodegenerative conditions in the absence of vascular risk factors, especially when considering their spatial distribution,” said senior author Ramón Landin-Romero, PhD, Appenzeller Neuroscience Fellow, Frontotemporal Dementia Research Group, University of Sydney.

“Clinicians can ask for specific sequences in routine MRI scans to visually detect WMH,” said Dr. Landin-Romero, who is also a senior lecturer in the School of Psychology and Brain and Mind Center.

The study was published online Feb. 17 in Neurology.
 

Difficult diagnosis

“FTD is a collection of unrecognized young-onset (before age 65) dementia syndromes that affect people in their prime,” said Dr. Landin-Romero. He added that heterogeneity in progression trajectories and symptoms, which can include changes in behavior and personality, language impairments, and psychosis, make it a difficult disease to diagnose.

“As such, our research was motivated by the need of sensitive and specific biomarkers of FTD, which are urgently needed to aid diagnosis, prognosis, and treatment development,” he said.

Previous research has been limited; there have only been a “handful” of cohort and case studies and studies involving individuals with mutations in one FTD-causative gene.

FTD is genetically and pathologically complex, and there has been no clear correlation between genetic mutations/underlying pathology and clinical presentation, Dr. Landin-Romero said.

WMH are common in older individuals and are linked to increased risk for cognitive impairment and dementia. Traditionally, they have been associated with vascular risk factors, such as smoking and diabetes. “But the presentation of WMH in FTD and its associations with the severity of symptoms and brain atrophy across FTD symptoms remains to be established,” said Dr. Landin-Romero.
 

Higher disease severity

To explore the possible association, the researchers studied 129 patients with either bvFTD (n = 64; mean age, 64 years) or Alzheimer’s disease (n = 65; mean age, 64.66 years).

Neuropsychological assessments, medical and neurologic examinations, clinical interview, and structural brain MRI were conducted for all patients, who were compared with 66 age-, sex-, and education-matched healthy control persons (mean age, 64.69 years).

Some participants in the FTD, Alzheimer’s disease, and healthy control groups (n = 54, 44, and 26, respectively) also underwent genetic screening. Postmortem pathology findings were available for a small number of FTD and Alzheimer’s disease participants (n = 13 and 5, respectively).

The medical history included lifestyle and cardiovascular risk factors, as well as other health and neurologic conditions and medication history. Hypertension, hypercholesterolemia, diabetes, and smoking were used to assess vascular risk.

The FTD and Alzheimer’s disease groups did not differ with regard to disease duration (3.55 years; standard deviation, 1.75, and 3.24 years; SD, 1.59, respectively). However, disease severity was significantly higher among those with FTD than among those with Alzheimer’s disease, as measured by the FTD Rating Scale Rasch score (–0.52; SD, 1.28, vs. 0.78; SD, 1.55; P < .001).

Compared with healthy controls, patients in the FTD and Alzheimer’s disease groups scored significantly lower on the Addenbrooke’s Cognitive Examination–Revised (ACE-R) or ACE-III scale. Patients with Alzheimer’s disease showed “disproportionately larger deficits” in memory and visuospatial processing, compared with those with FTD, whereas those with FTD performed significantly worse than those with Alzheimer’s disease in the fluency subdomain.

A larger number of patients in the FTD group screened positive for genetic abnormalities than in the Alzheimer’s disease group; no participants in the healthy control group had genetic mutations.
 

Unexpected findings

Mean WMH volume was significantly higher in participants with FTD than in participants with Alzheimer’s disease and in healthy controls (mean, 0.76 mL, 0.40 mL, and 0.12 mL respectively). These larger volumes contributed to greater disease severity and cortical atrophy. Moreover, disease severity was “found to be a strong predictor of WMH volume in FTD,” the authors stated. Among patients with FTD, WMH volumes did not differ significantly with regard to genetic mutation status or presence of strong family history.

After controlling for age, vascular risk did not significantly predict WMH volume in the FTD group (P = .16); however, that did not hold true in the Alzheimer’s disease group.

Increased WMH were associated with anterior brain regions in FTD and with posterior brain regions in Alzheimer’s disease. In both disorders, higher WMH volume in the corpus callosum was associated with poorer cognitive performance in the domain of attention.

“The spatial distribution of WMH mirrored patterns of brain atrophy in FTD and Alzheimer’s disease, was partially independent of cortical degeneration, and was correlated with cognitive deficits,” said Dr. Landin-Romero.

The findings were not what he and his research colleagues expected. “We were expecting that the amounts of WMH would be similar in FTD and Alzheimer’s disease, but we actually found higher levels in participants with FTD,” he said. Additionally, he anticipated that patients with either FTD or Alzheimer’s disease who had more severe disease would have more WMH, but that finding only held true for people with FTD.

“In sum, our findings show that WMH are a core feature of FTD and Alzheimer’s disease that can contribute to cognitive problems, and not simply as a marker of vascular disease,” said Dr. Landin-Romero.
 

Major research contribution

Commenting on the study, Jordi Matias-Guiu, PhD, MD, of the department of neurology, Hospital Clinico, San Carlos, Spain, considers the study to be a “great contribution to the field.” Dr. Matias-Guiu, who was not involved with the study, said that WMH “do not necessarily mean vascular pathology, and atrophy may partially explain these abnormalities and should be taken into account in the interpretation of brain MRI.

“WMH are present in both Alzheimer’s disease and FTD and are relevant to cognitive deficits found in these disorders,” he added.

The study was funded by grants from the National Health and Medical Research Council of Australia, the Dementia Research Team, and the ARC Center of Excellence in Cognition and Its Disorders. Dr. Landin-Romero is supported by the Appenzeller Neuroscience Fellowship in Alzheimer’s Disease and the ARC Center of Excellence in Cognition and Its Disorders Memory Program. The other authors’ disclosures are listed on the original article. Dr. Matias-Guiu reports no relevant financial relationships.

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

Increased white matter hyperintensities (WMH) are strongly associated with Alzheimer’s disease, but new research reveals they are also a “core feature” of frontotemporal dementia (FTD) in findings that may help physicians make this difficult diagnosis that affects adults in their prime.

“The assessment of WMH can aid differential diagnosis of bvFTD [behavioral-variant FTD] against other neurodegenerative conditions in the absence of vascular risk factors, especially when considering their spatial distribution,” said senior author Ramón Landin-Romero, PhD, Appenzeller Neuroscience Fellow, Frontotemporal Dementia Research Group, University of Sydney.

“Clinicians can ask for specific sequences in routine MRI scans to visually detect WMH,” said Dr. Landin-Romero, who is also a senior lecturer in the School of Psychology and Brain and Mind Center.

The study was published online Feb. 17 in Neurology.
 

Difficult diagnosis

“FTD is a collection of unrecognized young-onset (before age 65) dementia syndromes that affect people in their prime,” said Dr. Landin-Romero. He added that heterogeneity in progression trajectories and symptoms, which can include changes in behavior and personality, language impairments, and psychosis, make it a difficult disease to diagnose.

“As such, our research was motivated by the need of sensitive and specific biomarkers of FTD, which are urgently needed to aid diagnosis, prognosis, and treatment development,” he said.

Previous research has been limited; there have only been a “handful” of cohort and case studies and studies involving individuals with mutations in one FTD-causative gene.

FTD is genetically and pathologically complex, and there has been no clear correlation between genetic mutations/underlying pathology and clinical presentation, Dr. Landin-Romero said.

WMH are common in older individuals and are linked to increased risk for cognitive impairment and dementia. Traditionally, they have been associated with vascular risk factors, such as smoking and diabetes. “But the presentation of WMH in FTD and its associations with the severity of symptoms and brain atrophy across FTD symptoms remains to be established,” said Dr. Landin-Romero.
 

Higher disease severity

To explore the possible association, the researchers studied 129 patients with either bvFTD (n = 64; mean age, 64 years) or Alzheimer’s disease (n = 65; mean age, 64.66 years).

Neuropsychological assessments, medical and neurologic examinations, clinical interview, and structural brain MRI were conducted for all patients, who were compared with 66 age-, sex-, and education-matched healthy control persons (mean age, 64.69 years).

Some participants in the FTD, Alzheimer’s disease, and healthy control groups (n = 54, 44, and 26, respectively) also underwent genetic screening. Postmortem pathology findings were available for a small number of FTD and Alzheimer’s disease participants (n = 13 and 5, respectively).

The medical history included lifestyle and cardiovascular risk factors, as well as other health and neurologic conditions and medication history. Hypertension, hypercholesterolemia, diabetes, and smoking were used to assess vascular risk.

The FTD and Alzheimer’s disease groups did not differ with regard to disease duration (3.55 years; standard deviation, 1.75, and 3.24 years; SD, 1.59, respectively). However, disease severity was significantly higher among those with FTD than among those with Alzheimer’s disease, as measured by the FTD Rating Scale Rasch score (–0.52; SD, 1.28, vs. 0.78; SD, 1.55; P < .001).

Compared with healthy controls, patients in the FTD and Alzheimer’s disease groups scored significantly lower on the Addenbrooke’s Cognitive Examination–Revised (ACE-R) or ACE-III scale. Patients with Alzheimer’s disease showed “disproportionately larger deficits” in memory and visuospatial processing, compared with those with FTD, whereas those with FTD performed significantly worse than those with Alzheimer’s disease in the fluency subdomain.

A larger number of patients in the FTD group screened positive for genetic abnormalities than in the Alzheimer’s disease group; no participants in the healthy control group had genetic mutations.
 

Unexpected findings

Mean WMH volume was significantly higher in participants with FTD than in participants with Alzheimer’s disease and in healthy controls (mean, 0.76 mL, 0.40 mL, and 0.12 mL respectively). These larger volumes contributed to greater disease severity and cortical atrophy. Moreover, disease severity was “found to be a strong predictor of WMH volume in FTD,” the authors stated. Among patients with FTD, WMH volumes did not differ significantly with regard to genetic mutation status or presence of strong family history.

After controlling for age, vascular risk did not significantly predict WMH volume in the FTD group (P = .16); however, that did not hold true in the Alzheimer’s disease group.

Increased WMH were associated with anterior brain regions in FTD and with posterior brain regions in Alzheimer’s disease. In both disorders, higher WMH volume in the corpus callosum was associated with poorer cognitive performance in the domain of attention.

“The spatial distribution of WMH mirrored patterns of brain atrophy in FTD and Alzheimer’s disease, was partially independent of cortical degeneration, and was correlated with cognitive deficits,” said Dr. Landin-Romero.

The findings were not what he and his research colleagues expected. “We were expecting that the amounts of WMH would be similar in FTD and Alzheimer’s disease, but we actually found higher levels in participants with FTD,” he said. Additionally, he anticipated that patients with either FTD or Alzheimer’s disease who had more severe disease would have more WMH, but that finding only held true for people with FTD.

“In sum, our findings show that WMH are a core feature of FTD and Alzheimer’s disease that can contribute to cognitive problems, and not simply as a marker of vascular disease,” said Dr. Landin-Romero.
 

Major research contribution

Commenting on the study, Jordi Matias-Guiu, PhD, MD, of the department of neurology, Hospital Clinico, San Carlos, Spain, considers the study to be a “great contribution to the field.” Dr. Matias-Guiu, who was not involved with the study, said that WMH “do not necessarily mean vascular pathology, and atrophy may partially explain these abnormalities and should be taken into account in the interpretation of brain MRI.

“WMH are present in both Alzheimer’s disease and FTD and are relevant to cognitive deficits found in these disorders,” he added.

The study was funded by grants from the National Health and Medical Research Council of Australia, the Dementia Research Team, and the ARC Center of Excellence in Cognition and Its Disorders. Dr. Landin-Romero is supported by the Appenzeller Neuroscience Fellowship in Alzheimer’s Disease and the ARC Center of Excellence in Cognition and Its Disorders Memory Program. The other authors’ disclosures are listed on the original article. Dr. Matias-Guiu reports no relevant financial relationships.

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

This past year, the referrals to my private practice have taken a noticeable shift and caused me to pause.

HRAUN/Getty Images

More calls have come from nurses, many who work directly with COVID-19 patients, understandably seeking mental health treatment, or support. Especially in this time, nurses are facing trauma and stress that is unimaginable to many, myself included. Despite the collective efforts we have made as a society to recognize their work, I do not think we have given enough consideration to the enormous sacrifice nurses are currently undertaking to save our collective psyche.

As physicians and mental health providers, we have a glimpse into the complexities and stressors of medical treatment. In our line of work, we support patients with trauma on a regular basis. We feel deeply connected to patients, some of whom we have treated until the end of their lives. Despite that, I am not sure that I, or anyone, can truly comprehend what nurses face in today’s climate of care.

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com.

References

1. Rogers CR. J Consult Psychol. 1957;21(2):95-103.

2. Mallo CJ, Mintz DL. Psychodyn Psychiatry. 2013 Mar;41(1):13-37.

3. Resick PA et al. Cognitive Processing Therapy for PTSD: A Comprehensive Manual. Guilford Publications, 2016.

This past year, the referrals to my private practice have taken a noticeable shift and caused me to pause.

HRAUN/Getty Images

More calls have come from nurses, many who work directly with COVID-19 patients, understandably seeking mental health treatment, or support. Especially in this time, nurses are facing trauma and stress that is unimaginable to many, myself included. Despite the collective efforts we have made as a society to recognize their work, I do not think we have given enough consideration to the enormous sacrifice nurses are currently undertaking to save our collective psyche.

As physicians and mental health providers, we have a glimpse into the complexities and stressors of medical treatment. In our line of work, we support patients with trauma on a regular basis. We feel deeply connected to patients, some of whom we have treated until the end of their lives. Despite that, I am not sure that I, or anyone, can truly comprehend what nurses face in today’s climate of care.

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com.

References

1. Rogers CR. J Consult Psychol. 1957;21(2):95-103.

2. Mallo CJ, Mintz DL. Psychodyn Psychiatry. 2013 Mar;41(1):13-37.

3. Resick PA et al. Cognitive Processing Therapy for PTSD: A Comprehensive Manual. Guilford Publications, 2016.

This past year, the referrals to my private practice have taken a noticeable shift and caused me to pause.

HRAUN/Getty Images

More calls have come from nurses, many who work directly with COVID-19 patients, understandably seeking mental health treatment, or support. Especially in this time, nurses are facing trauma and stress that is unimaginable to many, myself included. Despite the collective efforts we have made as a society to recognize their work, I do not think we have given enough consideration to the enormous sacrifice nurses are currently undertaking to save our collective psyche.

As physicians and mental health providers, we have a glimpse into the complexities and stressors of medical treatment. In our line of work, we support patients with trauma on a regular basis. We feel deeply connected to patients, some of whom we have treated until the end of their lives. Despite that, I am not sure that I, or anyone, can truly comprehend what nurses face in today’s climate of care.

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com.

References

1. Rogers CR. J Consult Psychol. 1957;21(2):95-103.

2. Mallo CJ, Mintz DL. Psychodyn Psychiatry. 2013 Mar;41(1):13-37.

3. Resick PA et al. Cognitive Processing Therapy for PTSD: A Comprehensive Manual. Guilford Publications, 2016.

Researchers have come a long way in understanding the link between acute inflammation and treatment-resistant depression, but more work needs to be done, according to Mark Hyman Rapaport, MD.

Svisio/Thinkstock

“Inflammation has been a hot topic in the past decade, both because of its impact in medical disorders and in psychiatric disorders,” Dr. Rapaport, CEO of the Huntsman Mental Health Institute in Salt Lake City, Utah, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “We run into difficulty with chronic inflammation, which we see with rheumatic disorders, and when we think of metabolic syndrome and obesity.”

The immune system helps to control energy regulation and neuroendocrine function in acute inflammation and chronic inflammatory diseases. “We see a variety of effects on the central nervous system or liver function or on homeostasis of the body,” said Dr. Rapaport, who also chairs the department of psychiatry at the University of Utah, also in Salt Lake City. “These are all normal and necessary to channel energy to the immune system in order to fight what’s necessary in acute inflammatory response.”

A chronic state of inflammation can result in prolonged allocation of fuels to the immune system, tissue inflammation, and a chronically aberrant immune reaction, he continued. This can cause depressive symptoms/fatigue, anorexia, malnutrition, muscle wasting, cachectic obesity, insulin resistance, dyslipidemia, increased adipose tissue in the proximity of inflammatory lesion, alterations of steroid hormone axes, elevated sympathetic tone, hypertension, decreased parasympathetic tone, inflammation-related anemia, and osteopenia. “So, chronic inflammation has a lot of long-term sequelae that are detrimental,” he said.

Both physical stress and psychological stress also cause an inflammatory state. After looking at the medical literature, Dr. Rapaport and colleagues began to wonder whether inflammation and immune activation associated with psychiatric disorders are attributable to the stress of acute illness. To find out, they performed a meta-analysis of blood cytokine network alterations in psychiatric patients and evaluated comparisons between schizophrenia, bipolar disorder, and depression. A total of three meta-analyses were performed: one of acute/inpatient studies, one on the impact of acute treatment, and one of outpatient studies. The researchers hypothesized that inflammatory and immune findings in psychiatric illnesses were tied to two distinct etiologies: the acute stress of illness and intrinsic immune dysfunction.

The meta-analyses included 68 studies: 40 involving patients with schizophrenia, 18 involving those with major depressive disorder (MDD) and 10 involving those with bipolar disorder. The researchers found that levels of four cytokines were significantly increased in acutely ill patients with schizophrenia, bipolar mania, and MDD, compared with controls: interleukin-6, tumor necrosis factor–alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), and IL-1 receptor antagonist (IL-1RA). “There has not been a consistent blood panel used across studies, be it within a disorder itself like depression, or across disorders,” Dr. Rapaport noted. “This is a challenge that we face in looking at these data.”

Following treatment of acute illness, IL-6 levels significantly decreased in schizophrenia and MDD, but no significant changes in TNF-alpha levels were observed in patients with schizophrenia or MDD. In addition, sIL-2R levels increase in schizophrenia but remained unchanged in bipolar and MDD, while IL-1RA levels in bipolar mania decreased but remained unchanged in MDD. Meanwhile, assessment of the study’s 24 outpatient studies revealed that levels of IL-6 were significantly increased in outpatients with schizophrenia, euthymic bipolar disorder, and MDD, compared with controls (P < .01 for each). In addition, levels of IL-1 beta and sIL-2R were significantly increased in outpatients with schizophrenia and bipolar disorder.

According to Dr. Rapaport, these meta-analyses suggest that there are likely inflammatory immune findings present in acutely ill patients with MDD, schizophrenia, and bipolar disorder.

“Some of this activation decreases with effective acute treatment of the disorder,” he said. “The data suggest that immune changes are present in a subset of patients with all three disorders.”

Advancing this area of research requires a better understanding of the bidirectional interactions between the brain and periphery. “We also need to understand the regulatory role that microglia and astroglia play within the brain,” he said. “We need to identify changes in brain circuitry and function associated with inflammation and other immune changes. We also need to carefully scrutinize publications, understand the assumptions behind the statistics, and carry out more research beyond the protein level.”

He concluded his presentation by calling for research to help clinicians differentiate acute from chronic inflammation. “The study of both is important,” he said. “We need to understand the pathophysiology of immune changes in psychiatric disorders. We need to study both the triggers and pathways to resolution.”

Dr. Rapaport disclosed that he has received research support from the National Institutes of Health, the National Institute of Mental Health, and the National Center for Complementary and Integrative Health.

[email protected]

Researchers have come a long way in understanding the link between acute inflammation and treatment-resistant depression, but more work needs to be done, according to Mark Hyman Rapaport, MD.

Svisio/Thinkstock

“Inflammation has been a hot topic in the past decade, both because of its impact in medical disorders and in psychiatric disorders,” Dr. Rapaport, CEO of the Huntsman Mental Health Institute in Salt Lake City, Utah, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “We run into difficulty with chronic inflammation, which we see with rheumatic disorders, and when we think of metabolic syndrome and obesity.”

The immune system helps to control energy regulation and neuroendocrine function in acute inflammation and chronic inflammatory diseases. “We see a variety of effects on the central nervous system or liver function or on homeostasis of the body,” said Dr. Rapaport, who also chairs the department of psychiatry at the University of Utah, also in Salt Lake City. “These are all normal and necessary to channel energy to the immune system in order to fight what’s necessary in acute inflammatory response.”

A chronic state of inflammation can result in prolonged allocation of fuels to the immune system, tissue inflammation, and a chronically aberrant immune reaction, he continued. This can cause depressive symptoms/fatigue, anorexia, malnutrition, muscle wasting, cachectic obesity, insulin resistance, dyslipidemia, increased adipose tissue in the proximity of inflammatory lesion, alterations of steroid hormone axes, elevated sympathetic tone, hypertension, decreased parasympathetic tone, inflammation-related anemia, and osteopenia. “So, chronic inflammation has a lot of long-term sequelae that are detrimental,” he said.

Both physical stress and psychological stress also cause an inflammatory state. After looking at the medical literature, Dr. Rapaport and colleagues began to wonder whether inflammation and immune activation associated with psychiatric disorders are attributable to the stress of acute illness. To find out, they performed a meta-analysis of blood cytokine network alterations in psychiatric patients and evaluated comparisons between schizophrenia, bipolar disorder, and depression. A total of three meta-analyses were performed: one of acute/inpatient studies, one on the impact of acute treatment, and one of outpatient studies. The researchers hypothesized that inflammatory and immune findings in psychiatric illnesses were tied to two distinct etiologies: the acute stress of illness and intrinsic immune dysfunction.

The meta-analyses included 68 studies: 40 involving patients with schizophrenia, 18 involving those with major depressive disorder (MDD) and 10 involving those with bipolar disorder. The researchers found that levels of four cytokines were significantly increased in acutely ill patients with schizophrenia, bipolar mania, and MDD, compared with controls: interleukin-6, tumor necrosis factor–alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), and IL-1 receptor antagonist (IL-1RA). “There has not been a consistent blood panel used across studies, be it within a disorder itself like depression, or across disorders,” Dr. Rapaport noted. “This is a challenge that we face in looking at these data.”

Following treatment of acute illness, IL-6 levels significantly decreased in schizophrenia and MDD, but no significant changes in TNF-alpha levels were observed in patients with schizophrenia or MDD. In addition, sIL-2R levels increase in schizophrenia but remained unchanged in bipolar and MDD, while IL-1RA levels in bipolar mania decreased but remained unchanged in MDD. Meanwhile, assessment of the study’s 24 outpatient studies revealed that levels of IL-6 were significantly increased in outpatients with schizophrenia, euthymic bipolar disorder, and MDD, compared with controls (P < .01 for each). In addition, levels of IL-1 beta and sIL-2R were significantly increased in outpatients with schizophrenia and bipolar disorder.

According to Dr. Rapaport, these meta-analyses suggest that there are likely inflammatory immune findings present in acutely ill patients with MDD, schizophrenia, and bipolar disorder.

“Some of this activation decreases with effective acute treatment of the disorder,” he said. “The data suggest that immune changes are present in a subset of patients with all three disorders.”

Advancing this area of research requires a better understanding of the bidirectional interactions between the brain and periphery. “We also need to understand the regulatory role that microglia and astroglia play within the brain,” he said. “We need to identify changes in brain circuitry and function associated with inflammation and other immune changes. We also need to carefully scrutinize publications, understand the assumptions behind the statistics, and carry out more research beyond the protein level.”

He concluded his presentation by calling for research to help clinicians differentiate acute from chronic inflammation. “The study of both is important,” he said. “We need to understand the pathophysiology of immune changes in psychiatric disorders. We need to study both the triggers and pathways to resolution.”

Dr. Rapaport disclosed that he has received research support from the National Institutes of Health, the National Institute of Mental Health, and the National Center for Complementary and Integrative Health.

[email protected]

Researchers have come a long way in understanding the link between acute inflammation and treatment-resistant depression, but more work needs to be done, according to Mark Hyman Rapaport, MD.

Svisio/Thinkstock

“Inflammation has been a hot topic in the past decade, both because of its impact in medical disorders and in psychiatric disorders,” Dr. Rapaport, CEO of the Huntsman Mental Health Institute in Salt Lake City, Utah, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “We run into difficulty with chronic inflammation, which we see with rheumatic disorders, and when we think of metabolic syndrome and obesity.”

The immune system helps to control energy regulation and neuroendocrine function in acute inflammation and chronic inflammatory diseases. “We see a variety of effects on the central nervous system or liver function or on homeostasis of the body,” said Dr. Rapaport, who also chairs the department of psychiatry at the University of Utah, also in Salt Lake City. “These are all normal and necessary to channel energy to the immune system in order to fight what’s necessary in acute inflammatory response.”

A chronic state of inflammation can result in prolonged allocation of fuels to the immune system, tissue inflammation, and a chronically aberrant immune reaction, he continued. This can cause depressive symptoms/fatigue, anorexia, malnutrition, muscle wasting, cachectic obesity, insulin resistance, dyslipidemia, increased adipose tissue in the proximity of inflammatory lesion, alterations of steroid hormone axes, elevated sympathetic tone, hypertension, decreased parasympathetic tone, inflammation-related anemia, and osteopenia. “So, chronic inflammation has a lot of long-term sequelae that are detrimental,” he said.

Both physical stress and psychological stress also cause an inflammatory state. After looking at the medical literature, Dr. Rapaport and colleagues began to wonder whether inflammation and immune activation associated with psychiatric disorders are attributable to the stress of acute illness. To find out, they performed a meta-analysis of blood cytokine network alterations in psychiatric patients and evaluated comparisons between schizophrenia, bipolar disorder, and depression. A total of three meta-analyses were performed: one of acute/inpatient studies, one on the impact of acute treatment, and one of outpatient studies. The researchers hypothesized that inflammatory and immune findings in psychiatric illnesses were tied to two distinct etiologies: the acute stress of illness and intrinsic immune dysfunction.

The meta-analyses included 68 studies: 40 involving patients with schizophrenia, 18 involving those with major depressive disorder (MDD) and 10 involving those with bipolar disorder. The researchers found that levels of four cytokines were significantly increased in acutely ill patients with schizophrenia, bipolar mania, and MDD, compared with controls: interleukin-6, tumor necrosis factor–alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), and IL-1 receptor antagonist (IL-1RA). “There has not been a consistent blood panel used across studies, be it within a disorder itself like depression, or across disorders,” Dr. Rapaport noted. “This is a challenge that we face in looking at these data.”

Following treatment of acute illness, IL-6 levels significantly decreased in schizophrenia and MDD, but no significant changes in TNF-alpha levels were observed in patients with schizophrenia or MDD. In addition, sIL-2R levels increase in schizophrenia but remained unchanged in bipolar and MDD, while IL-1RA levels in bipolar mania decreased but remained unchanged in MDD. Meanwhile, assessment of the study’s 24 outpatient studies revealed that levels of IL-6 were significantly increased in outpatients with schizophrenia, euthymic bipolar disorder, and MDD, compared with controls (P < .01 for each). In addition, levels of IL-1 beta and sIL-2R were significantly increased in outpatients with schizophrenia and bipolar disorder.

According to Dr. Rapaport, these meta-analyses suggest that there are likely inflammatory immune findings present in acutely ill patients with MDD, schizophrenia, and bipolar disorder.

“Some of this activation decreases with effective acute treatment of the disorder,” he said. “The data suggest that immune changes are present in a subset of patients with all three disorders.”

Advancing this area of research requires a better understanding of the bidirectional interactions between the brain and periphery. “We also need to understand the regulatory role that microglia and astroglia play within the brain,” he said. “We need to identify changes in brain circuitry and function associated with inflammation and other immune changes. We also need to carefully scrutinize publications, understand the assumptions behind the statistics, and carry out more research beyond the protein level.”

He concluded his presentation by calling for research to help clinicians differentiate acute from chronic inflammation. “The study of both is important,” he said. “We need to understand the pathophysiology of immune changes in psychiatric disorders. We need to study both the triggers and pathways to resolution.”

Dr. Rapaport disclosed that he has received research support from the National Institutes of Health, the National Institute of Mental Health, and the National Center for Complementary and Integrative Health.

[email protected]