Neurology

Estimating an individual’s risk of cardiovascular disease (CVD) remains the cornerstone of the 2021 European Society of Cardiology guidelines on CVD prevention in clinical practice. The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.   

They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.

“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
 

Prevention at the individual and population levels

The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.

The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.

The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.

Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.

However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.

The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.

The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.

For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.

Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.

Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.

Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.

They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.

They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.

Potential cost issues that could be considered when implementing the guidelines are also reviewed.

Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
 

Setting the bar lower?

Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”

Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”

“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.

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

Estimating an individual’s risk of cardiovascular disease (CVD) remains the cornerstone of the 2021 European Society of Cardiology guidelines on CVD prevention in clinical practice. The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.   

They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.

“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
 

Prevention at the individual and population levels

The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.

The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.

The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.

Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.

However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.

The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.

The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.

For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.

Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.

Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.

Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.

They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.

They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.

Potential cost issues that could be considered when implementing the guidelines are also reviewed.

Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
 

Setting the bar lower?

Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”

Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”

“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.

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

Estimating an individual’s risk of cardiovascular disease (CVD) remains the cornerstone of the 2021 European Society of Cardiology guidelines on CVD prevention in clinical practice. The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.   

They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.

“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
 

Prevention at the individual and population levels

The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.

The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.

The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.

Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.

However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.

The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.

The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.

For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.

Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.

Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.

Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.

They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.

They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.

Potential cost issues that could be considered when implementing the guidelines are also reviewed.

Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
 

Setting the bar lower?

Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”

Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”

“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.

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

The brain is inarguably the most complex and mysterious organ in the human body.

As the epicenter of intelligence, mastermind of movement, and song for our senses, the brain is more than a 3-lb organ encased in shell and fluid. Rather, it is the crown jewel that defines the self and, broadly, humanity.

©Thinkstock

For decades now, researchers have been exploring the potential for connecting our own astounding biological “computer” with actual physical mainframes. These so-called “brain-computer interfaces” (BCIs) are showing promise in treating an array of conditions, including paralysis, deafness, stroke, and even psychiatric disorders.

Among the big players in this area of research is billionaire entrepreneur Elon Musk, who in 2016 founded Neuralink. The company’s short-term mission is to develop a brain-to-machine interface to help people with neurologic conditions (for example, Parkinson’s disease). The long-term mission is to steer humanity into the era of “superhuman cognition.”

But first, some neuroscience 101.

Neurons are specialized cells that transmit and receive information. The basic structure of a neuron includes the dendrite, soma, and axon. The dendrite is the signal receiver. The soma is the cell body that is connected to the dendrites and serves as a structure to pass signals. The axon, also known as the nerve fiber, transmits the signal away from the soma.

Neurons communicate with each other at the synapse (for example, axon-dendrite connection). Neurons send information to each other through action potentials. An action potential may be defined as an electric impulse that transmits down the axon, causing the release of neurotransmitters, which may consequently either inhibit or excite the next neuron (leading to the initiation of another action potential).

So how will the company and other BCI companies tap into this evolutionarily ancient system to develop an implant that will obtain and decode information output from the brain?

The Neuralink implant is composed of three parts: The Link, neural threads, and the charger.

A robotic system, controlled by a neurosurgeon, will place an implant into the brain. The Link is the central component. It processes and transmits neural signals. The micron-scale neural threads are connected to the Link and other areas of the brain. The threads also contain electrodes, which are responsible for detecting neural signals. The charger ensures the battery is charged via wireless connection.

The invasive nature of this implant allows for precise readouts of electric outputs from the brain – unlike noninvasive devices, which are less sensitive and specific. Additionally, owing to its small size, engineers and neurosurgeons can implant the device in very specific brain regions as well as customize electrode distribution.

The Neuralink implant would be paired with an application via Bluetooth connection. The goal is to enable someone with the implant to control their device or computer by simply thinking. The application offers several exercises to help guide and train individuals on how to use the implant for its intended purpose. This technology would allow people with neurologic difficulties (for example, paralysis) to communicate more easily through text or speech synthesis, as well as partake in creative activities such as photography.

Existing text and speech synthesis technology are already underway. For example, Synchron, a BCI platform company, is investigating the use of Stentrode for people with severe paralysis. This neuroprosthesis was designed to help people associate thought with movement through Bluetooth technology (for example, texting, emailing, shopping, online banking). Preliminary results from a study in which the device was used for patients with amyotrophic lateral sclerosis showed improvements in functional independence via direct thinking.

Software intended to enable high-performance handwriting utilizing BCI technology is being developed by Francis R. Willett, PhD, at Stanford (Calif.) University. The technology has also shown promise.

“We’ve learned that the brain retains its ability to prescribe fine movements a full decade after the body has lost its ability to execute those movements,” says Dr. Willett, who recently reported on results from a BCI study of handwriting conversion in an individual with full-body paralysis. Through a recurrent neural networking decoding approach, the BrainGate study participant was able to type 90 characters per minute – with an impressive 94.1% raw accuracy – using thoughts alone.

Although not a fully implantable brain device, this percutaneous implant has also been studied of its capacity to restore arm function among individuals who suffered from chronic stroke. Preliminary results from the Cortimo trials, led by Mijail D. Serruya, MD, an assistant professor at Thomas Jefferson University, Philadelphia, have been positive. Researchers implanted microelectrode arrays to decode brain signals and power motor function in a participant who had experienced a stroke 2 years earlier. The participant was able to use a powered arm brace on their paralyzed arm.

Neuralink recently released a video demonstrating the use of the interface in a monkey named Pager as it played a game with a joystick. Company researchers inserted a 1024-Electrode neural recording and data transmission device called the N1 Link into the left and right motor cortices. Using the implant, neural activity was sent to a decoder algorithm. Throughout the process, the decoder algorithm was refined and calibrated. After a few minutes, Pager was able to control the cursor on the screen using his mind instead of the joystick.

Mr. Musk hopes to develop Neuralink further to change not only the way we treat neurological disorders but also the way we interact with ourselves and our environment. It’s a lofty goal to be sure, but one that doesn’t seem outside the realm of possibility in the near future.
 

Known unknowns: The ethical dilemmas

One major conundrum facing the future of BCI technology is that researchers don’t fully understand the science regarding how brain signaling, artificial intelligence (AI) software, and prostheses interact. Although offloading computations improves the predictive nature of AI algorithms, there are concerns of identity and personal agency.

How do we know that an action is truly the result of one’s own thinking or, rather, the outcome of AI software? In this context, the autocorrect function while typing can be incredibly useful when we’re in a pinch for time, when we’re using one hand to type, or because of ease. However, it’s also easy to create and send out unintended or inappropriate messages.

These algorithms are designed to learn from our behavior and anticipate our next move. However, a question arises as to whether we are the authors of our own thoughts or whether we are simply the device that delivers messages under the control of external forces.

“People may question whether new personality changes they experience are truly representative of themselves or whether they are now a product of the implant (e.g., ‘Is that really me?’; ‘Have I grown as a person, or is it the technology?’). This then raises questions about agency and who we are as people,” says Kerry Bowman, PhD, a clinical bioethicist and assistant professor at the Temerty Faculty of Medicine of the University of Toronto.

It’s important to have safeguards in place to ensure the privacy of our thoughts. In an age where data is currency, it’s crucial to establish boundaries to preserve our autonomy and prevent exploitation (for example, by private companies or hackers). Although Neuralink and BCIs generally are certainly pushing the boundaries of neural engineering in profound ways, it’s important to note the biological and ethical implications of this technology.

As Dr. Bowman points out, “throughout the entire human story, under the worst of human circumstances, such as captivity and torture, the one safe ground and place for all people has been the privacy of one’s own mind. No one could ever interfere, take away, or be aware of those thoughts. However, this technology challenges one’s own privacy – that this technology (and, by extension, a company) could be aware of those thoughts.”

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

The brain is inarguably the most complex and mysterious organ in the human body.

As the epicenter of intelligence, mastermind of movement, and song for our senses, the brain is more than a 3-lb organ encased in shell and fluid. Rather, it is the crown jewel that defines the self and, broadly, humanity.

©Thinkstock

For decades now, researchers have been exploring the potential for connecting our own astounding biological “computer” with actual physical mainframes. These so-called “brain-computer interfaces” (BCIs) are showing promise in treating an array of conditions, including paralysis, deafness, stroke, and even psychiatric disorders.

Among the big players in this area of research is billionaire entrepreneur Elon Musk, who in 2016 founded Neuralink. The company’s short-term mission is to develop a brain-to-machine interface to help people with neurologic conditions (for example, Parkinson’s disease). The long-term mission is to steer humanity into the era of “superhuman cognition.”

But first, some neuroscience 101.

Neurons are specialized cells that transmit and receive information. The basic structure of a neuron includes the dendrite, soma, and axon. The dendrite is the signal receiver. The soma is the cell body that is connected to the dendrites and serves as a structure to pass signals. The axon, also known as the nerve fiber, transmits the signal away from the soma.

Neurons communicate with each other at the synapse (for example, axon-dendrite connection). Neurons send information to each other through action potentials. An action potential may be defined as an electric impulse that transmits down the axon, causing the release of neurotransmitters, which may consequently either inhibit or excite the next neuron (leading to the initiation of another action potential).

So how will the company and other BCI companies tap into this evolutionarily ancient system to develop an implant that will obtain and decode information output from the brain?

The Neuralink implant is composed of three parts: The Link, neural threads, and the charger.

A robotic system, controlled by a neurosurgeon, will place an implant into the brain. The Link is the central component. It processes and transmits neural signals. The micron-scale neural threads are connected to the Link and other areas of the brain. The threads also contain electrodes, which are responsible for detecting neural signals. The charger ensures the battery is charged via wireless connection.

The invasive nature of this implant allows for precise readouts of electric outputs from the brain – unlike noninvasive devices, which are less sensitive and specific. Additionally, owing to its small size, engineers and neurosurgeons can implant the device in very specific brain regions as well as customize electrode distribution.

The Neuralink implant would be paired with an application via Bluetooth connection. The goal is to enable someone with the implant to control their device or computer by simply thinking. The application offers several exercises to help guide and train individuals on how to use the implant for its intended purpose. This technology would allow people with neurologic difficulties (for example, paralysis) to communicate more easily through text or speech synthesis, as well as partake in creative activities such as photography.

Existing text and speech synthesis technology are already underway. For example, Synchron, a BCI platform company, is investigating the use of Stentrode for people with severe paralysis. This neuroprosthesis was designed to help people associate thought with movement through Bluetooth technology (for example, texting, emailing, shopping, online banking). Preliminary results from a study in which the device was used for patients with amyotrophic lateral sclerosis showed improvements in functional independence via direct thinking.

Software intended to enable high-performance handwriting utilizing BCI technology is being developed by Francis R. Willett, PhD, at Stanford (Calif.) University. The technology has also shown promise.

“We’ve learned that the brain retains its ability to prescribe fine movements a full decade after the body has lost its ability to execute those movements,” says Dr. Willett, who recently reported on results from a BCI study of handwriting conversion in an individual with full-body paralysis. Through a recurrent neural networking decoding approach, the BrainGate study participant was able to type 90 characters per minute – with an impressive 94.1% raw accuracy – using thoughts alone.

Although not a fully implantable brain device, this percutaneous implant has also been studied of its capacity to restore arm function among individuals who suffered from chronic stroke. Preliminary results from the Cortimo trials, led by Mijail D. Serruya, MD, an assistant professor at Thomas Jefferson University, Philadelphia, have been positive. Researchers implanted microelectrode arrays to decode brain signals and power motor function in a participant who had experienced a stroke 2 years earlier. The participant was able to use a powered arm brace on their paralyzed arm.

Neuralink recently released a video demonstrating the use of the interface in a monkey named Pager as it played a game with a joystick. Company researchers inserted a 1024-Electrode neural recording and data transmission device called the N1 Link into the left and right motor cortices. Using the implant, neural activity was sent to a decoder algorithm. Throughout the process, the decoder algorithm was refined and calibrated. After a few minutes, Pager was able to control the cursor on the screen using his mind instead of the joystick.

Mr. Musk hopes to develop Neuralink further to change not only the way we treat neurological disorders but also the way we interact with ourselves and our environment. It’s a lofty goal to be sure, but one that doesn’t seem outside the realm of possibility in the near future.
 

Known unknowns: The ethical dilemmas

One major conundrum facing the future of BCI technology is that researchers don’t fully understand the science regarding how brain signaling, artificial intelligence (AI) software, and prostheses interact. Although offloading computations improves the predictive nature of AI algorithms, there are concerns of identity and personal agency.

How do we know that an action is truly the result of one’s own thinking or, rather, the outcome of AI software? In this context, the autocorrect function while typing can be incredibly useful when we’re in a pinch for time, when we’re using one hand to type, or because of ease. However, it’s also easy to create and send out unintended or inappropriate messages.

These algorithms are designed to learn from our behavior and anticipate our next move. However, a question arises as to whether we are the authors of our own thoughts or whether we are simply the device that delivers messages under the control of external forces.

“People may question whether new personality changes they experience are truly representative of themselves or whether they are now a product of the implant (e.g., ‘Is that really me?’; ‘Have I grown as a person, or is it the technology?’). This then raises questions about agency and who we are as people,” says Kerry Bowman, PhD, a clinical bioethicist and assistant professor at the Temerty Faculty of Medicine of the University of Toronto.

It’s important to have safeguards in place to ensure the privacy of our thoughts. In an age where data is currency, it’s crucial to establish boundaries to preserve our autonomy and prevent exploitation (for example, by private companies or hackers). Although Neuralink and BCIs generally are certainly pushing the boundaries of neural engineering in profound ways, it’s important to note the biological and ethical implications of this technology.

As Dr. Bowman points out, “throughout the entire human story, under the worst of human circumstances, such as captivity and torture, the one safe ground and place for all people has been the privacy of one’s own mind. No one could ever interfere, take away, or be aware of those thoughts. However, this technology challenges one’s own privacy – that this technology (and, by extension, a company) could be aware of those thoughts.”

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

The brain is inarguably the most complex and mysterious organ in the human body.

As the epicenter of intelligence, mastermind of movement, and song for our senses, the brain is more than a 3-lb organ encased in shell and fluid. Rather, it is the crown jewel that defines the self and, broadly, humanity.

©Thinkstock

For decades now, researchers have been exploring the potential for connecting our own astounding biological “computer” with actual physical mainframes. These so-called “brain-computer interfaces” (BCIs) are showing promise in treating an array of conditions, including paralysis, deafness, stroke, and even psychiatric disorders.

Among the big players in this area of research is billionaire entrepreneur Elon Musk, who in 2016 founded Neuralink. The company’s short-term mission is to develop a brain-to-machine interface to help people with neurologic conditions (for example, Parkinson’s disease). The long-term mission is to steer humanity into the era of “superhuman cognition.”

But first, some neuroscience 101.

Neurons are specialized cells that transmit and receive information. The basic structure of a neuron includes the dendrite, soma, and axon. The dendrite is the signal receiver. The soma is the cell body that is connected to the dendrites and serves as a structure to pass signals. The axon, also known as the nerve fiber, transmits the signal away from the soma.

Neurons communicate with each other at the synapse (for example, axon-dendrite connection). Neurons send information to each other through action potentials. An action potential may be defined as an electric impulse that transmits down the axon, causing the release of neurotransmitters, which may consequently either inhibit or excite the next neuron (leading to the initiation of another action potential).

So how will the company and other BCI companies tap into this evolutionarily ancient system to develop an implant that will obtain and decode information output from the brain?

The Neuralink implant is composed of three parts: The Link, neural threads, and the charger.

A robotic system, controlled by a neurosurgeon, will place an implant into the brain. The Link is the central component. It processes and transmits neural signals. The micron-scale neural threads are connected to the Link and other areas of the brain. The threads also contain electrodes, which are responsible for detecting neural signals. The charger ensures the battery is charged via wireless connection.

The invasive nature of this implant allows for precise readouts of electric outputs from the brain – unlike noninvasive devices, which are less sensitive and specific. Additionally, owing to its small size, engineers and neurosurgeons can implant the device in very specific brain regions as well as customize electrode distribution.

The Neuralink implant would be paired with an application via Bluetooth connection. The goal is to enable someone with the implant to control their device or computer by simply thinking. The application offers several exercises to help guide and train individuals on how to use the implant for its intended purpose. This technology would allow people with neurologic difficulties (for example, paralysis) to communicate more easily through text or speech synthesis, as well as partake in creative activities such as photography.

Existing text and speech synthesis technology are already underway. For example, Synchron, a BCI platform company, is investigating the use of Stentrode for people with severe paralysis. This neuroprosthesis was designed to help people associate thought with movement through Bluetooth technology (for example, texting, emailing, shopping, online banking). Preliminary results from a study in which the device was used for patients with amyotrophic lateral sclerosis showed improvements in functional independence via direct thinking.

Software intended to enable high-performance handwriting utilizing BCI technology is being developed by Francis R. Willett, PhD, at Stanford (Calif.) University. The technology has also shown promise.

“We’ve learned that the brain retains its ability to prescribe fine movements a full decade after the body has lost its ability to execute those movements,” says Dr. Willett, who recently reported on results from a BCI study of handwriting conversion in an individual with full-body paralysis. Through a recurrent neural networking decoding approach, the BrainGate study participant was able to type 90 characters per minute – with an impressive 94.1% raw accuracy – using thoughts alone.

Although not a fully implantable brain device, this percutaneous implant has also been studied of its capacity to restore arm function among individuals who suffered from chronic stroke. Preliminary results from the Cortimo trials, led by Mijail D. Serruya, MD, an assistant professor at Thomas Jefferson University, Philadelphia, have been positive. Researchers implanted microelectrode arrays to decode brain signals and power motor function in a participant who had experienced a stroke 2 years earlier. The participant was able to use a powered arm brace on their paralyzed arm.

Neuralink recently released a video demonstrating the use of the interface in a monkey named Pager as it played a game with a joystick. Company researchers inserted a 1024-Electrode neural recording and data transmission device called the N1 Link into the left and right motor cortices. Using the implant, neural activity was sent to a decoder algorithm. Throughout the process, the decoder algorithm was refined and calibrated. After a few minutes, Pager was able to control the cursor on the screen using his mind instead of the joystick.

Mr. Musk hopes to develop Neuralink further to change not only the way we treat neurological disorders but also the way we interact with ourselves and our environment. It’s a lofty goal to be sure, but one that doesn’t seem outside the realm of possibility in the near future.
 

Known unknowns: The ethical dilemmas

One major conundrum facing the future of BCI technology is that researchers don’t fully understand the science regarding how brain signaling, artificial intelligence (AI) software, and prostheses interact. Although offloading computations improves the predictive nature of AI algorithms, there are concerns of identity and personal agency.

How do we know that an action is truly the result of one’s own thinking or, rather, the outcome of AI software? In this context, the autocorrect function while typing can be incredibly useful when we’re in a pinch for time, when we’re using one hand to type, or because of ease. However, it’s also easy to create and send out unintended or inappropriate messages.

These algorithms are designed to learn from our behavior and anticipate our next move. However, a question arises as to whether we are the authors of our own thoughts or whether we are simply the device that delivers messages under the control of external forces.

“People may question whether new personality changes they experience are truly representative of themselves or whether they are now a product of the implant (e.g., ‘Is that really me?’; ‘Have I grown as a person, or is it the technology?’). This then raises questions about agency and who we are as people,” says Kerry Bowman, PhD, a clinical bioethicist and assistant professor at the Temerty Faculty of Medicine of the University of Toronto.

It’s important to have safeguards in place to ensure the privacy of our thoughts. In an age where data is currency, it’s crucial to establish boundaries to preserve our autonomy and prevent exploitation (for example, by private companies or hackers). Although Neuralink and BCIs generally are certainly pushing the boundaries of neural engineering in profound ways, it’s important to note the biological and ethical implications of this technology.

As Dr. Bowman points out, “throughout the entire human story, under the worst of human circumstances, such as captivity and torture, the one safe ground and place for all people has been the privacy of one’s own mind. No one could ever interfere, take away, or be aware of those thoughts. However, this technology challenges one’s own privacy – that this technology (and, by extension, a company) could be aware of those thoughts.”

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

Background: Falls are the leading cause of unintentional injuries and injury-related deaths among adults aged 65 years and older. FRIDs (such as antidepressants, sedatives-hypnotics, and opioids) continue to be a major contributor for risk of falls. At the same time, little is known about prevalence of use or interventions directed toward reduction of use in older adults presenting with fall.

Limitations of this review included high risk of bias in observational studies and unclear timeline definitions of interventions or outcome measurements in the intervention studies. In conclusion, there is a significant need for well-designed interventions targeted at reducing FRID use in conjunction with other risk factors to decrease the incidence of falls comprehensively. An aggressive approach directed toward patient education along with primary care communication may be the key to reducing FRID use in this population.

Bottom line: With limited evidence, there is a high prevalence of FRID use in older adults presenting with falls and no reduction in FRID use following the encounter.

Citation: Hart LA et al. Use of fall risk-increasing drugs around a fall-related injury in older adults: A systematic review. J Am Geriatr Soc. 2020 Feb 17. doi: 10.1111/jgs.16369.

Dr. Yarra is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Falls are the leading cause of unintentional injuries and injury-related deaths among adults aged 65 years and older. FRIDs (such as antidepressants, sedatives-hypnotics, and opioids) continue to be a major contributor for risk of falls. At the same time, little is known about prevalence of use or interventions directed toward reduction of use in older adults presenting with fall.

Limitations of this review included high risk of bias in observational studies and unclear timeline definitions of interventions or outcome measurements in the intervention studies. In conclusion, there is a significant need for well-designed interventions targeted at reducing FRID use in conjunction with other risk factors to decrease the incidence of falls comprehensively. An aggressive approach directed toward patient education along with primary care communication may be the key to reducing FRID use in this population.

Bottom line: With limited evidence, there is a high prevalence of FRID use in older adults presenting with falls and no reduction in FRID use following the encounter.

Citation: Hart LA et al. Use of fall risk-increasing drugs around a fall-related injury in older adults: A systematic review. J Am Geriatr Soc. 2020 Feb 17. doi: 10.1111/jgs.16369.

Dr. Yarra is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Falls are the leading cause of unintentional injuries and injury-related deaths among adults aged 65 years and older. FRIDs (such as antidepressants, sedatives-hypnotics, and opioids) continue to be a major contributor for risk of falls. At the same time, little is known about prevalence of use or interventions directed toward reduction of use in older adults presenting with fall.

Limitations of this review included high risk of bias in observational studies and unclear timeline definitions of interventions or outcome measurements in the intervention studies. In conclusion, there is a significant need for well-designed interventions targeted at reducing FRID use in conjunction with other risk factors to decrease the incidence of falls comprehensively. An aggressive approach directed toward patient education along with primary care communication may be the key to reducing FRID use in this population.

Bottom line: With limited evidence, there is a high prevalence of FRID use in older adults presenting with falls and no reduction in FRID use following the encounter.

Citation: Hart LA et al. Use of fall risk-increasing drugs around a fall-related injury in older adults: A systematic review. J Am Geriatr Soc. 2020 Feb 17. doi: 10.1111/jgs.16369.

Dr. Yarra is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

People with multiple sclerosis (MS) and depression have an increased risk of death, compared with those with one or neither condition, as well as an increased risk of vascular disease, a new study has found. “The effects of depression and MS on all-cause mortality are synergistic,” wrote lead author Raffaele Palladino, MD, PhD, research associate, faculty of medicine, Imperial College London.

The study was published in Neurology.

To assess the association between depression, vascular disease, and death in patients with MS, the researchers launched a population-based retrospective cohort study that reviewed English medical records from January 1987 to December 2018 and matched people with and without MS. Ultimately, 12,251 people with MS were matched with 72,572 controls. At baseline, 21% of the MS group (n = 2,535) and 9% of the controls (n = 6,278) had depression. Women were the majority in both cohorts and were more likely than men to be depressed.

People with both MS and depression had an all-cause mortality rate of 10.3 cases per 100,000 person-years (95% confidence interval, 9.17-11.57), compared with 10.6 for people with MS without depression (95% CI, 9.99-11.21), 3.6 for people with depression but not MS (95% CI, 3.18-4.05), and 2.5 for people with neither condition (95% CI, 2.42-2.64). Compared with controls without depression, the 10-year hazard of all-cause mortality was increasingly greater in controls with depression (hazard ratio, 1.75; 95% CI, 1.59-1.91), people with MS but not depression (HR, 3.88; 95% CI, 3.66-4.10), and people with MS and depression (HR, 5.43; 95% CI, 4.88-5.96). Overall, 14% of the observed effect on mortality was attributable to the interaction between MS status and depression.

As for vascular diseases, people with MS had an increased risk regardless of their depression status. That said, people with MS and depression (HR, 3.30; 95% CI, 2.37-4.23) had a notably higher risk than people with MS and no depression (HR, 1.48; 95% CI, 1.23-1.74). Women with MS and depression also had a greater risk of vascular disease than women with MS and no depression, while men with MS did not have significantly different risks of acute coronary syndrome or composite macrovascular disease than those in the control group who did not suffer from depression.
 

Does treating depression decrease the likelihood of vascular disease?

“The take-home message for me is the importance of treating depression in this population, in which we see it with great regularity,” Joseph Berger, MD, professor of neurology and associate chief of the multiple sclerosis division at the University of Pennsylvania, Philadelphia, said in an interview. “The question that I have is: If you treat depression in an individual with MS or an individual who is simply depressed and thus at risk for the subsequent development of vascular disease, does it decrease the likelihood of their subsequent development of vascular disease in comparison to had you not?

“I presume it does,” he added, noting that “the theories underlying why depression would increase one’s risk of subsequent vascular disease are enumerated by the authors, including such things as increased inflammation. Now, the inflammation may be contributing to the depression, or the depression may be contributing to the inflammation; it may be one of those chicken-and-egg scenarios. But if you decrease the depression, do you thereby decrease the inflammation, which has a pernicious effect on endothelial cells and increases one’s vascular risk?

“Alternatively, lifestyle in depressed patients is also altered,” he said. “They’re far less likely to engage in exercise, healthy habits, and healthy diets, and more likely perhaps to smoke. These all need to be addressed, but this study certainly gives you a greater impetus as a MS neurologist to address the issue of depression, realizing that there is also this comorbidity of vascular disease.”
 

Evaluating the biological interaction between MS and depression

Based on this and other studies, the joint effect of MS and depression on all-cause mortality may qualify as a biological interaction, Amber Salter, PhD, of the University of Texas Southwestern Medical Center, Dallas, wrote in an accompanying editorial.

“Biological interactions consider whether the joint effect of two factors follow an additive pattern, or the joint effect of two factors is greater than the sum of the individual effects for each factor alone,” she wrote. And though the interaction was not found to be present for vascular disease and cardiovascular mortality, it was for all-cause mortality.

“When warranted, the evaluation of biological interactions in future studies should be considered to provide insight on target subpopulations for interventions or test for potential mechanistic forms of interaction,” she added.

Dr. Salter highlighted the study’s strengths, including a large sample size and six controls matched to each MS patient. She also stated that the researchers’ inability to control for risk factors like body mass index and physical activity means the 14% increase in mortality “may not be a large absolute increase in mortality when other covariates cannot be considered.” In addition, their lack of data on suicide – and its association with depression – offers up the possibility that increases in mortality could be tied to a “potentially modifiable risk” as opposed to a biologically increased one.

In acknowledging their study’s limitations, the authors stated that body mass index, though an important vascular risk factor, has a “modest” association with mortality, and that the average annual suicide rate in the MS population – though higher than in the non-MS population – is still “relatively low.”

Two of the authors disclosed receiving support, including grants and research funding, from various institutions and organizations in the United Kingdom, the United States, and Canada, as well as several pharmaceutical companies. Dr. Salter reported no relevant disclosures.

People with multiple sclerosis (MS) and depression have an increased risk of death, compared with those with one or neither condition, as well as an increased risk of vascular disease, a new study has found. “The effects of depression and MS on all-cause mortality are synergistic,” wrote lead author Raffaele Palladino, MD, PhD, research associate, faculty of medicine, Imperial College London.

The study was published in Neurology.

To assess the association between depression, vascular disease, and death in patients with MS, the researchers launched a population-based retrospective cohort study that reviewed English medical records from January 1987 to December 2018 and matched people with and without MS. Ultimately, 12,251 people with MS were matched with 72,572 controls. At baseline, 21% of the MS group (n = 2,535) and 9% of the controls (n = 6,278) had depression. Women were the majority in both cohorts and were more likely than men to be depressed.

People with both MS and depression had an all-cause mortality rate of 10.3 cases per 100,000 person-years (95% confidence interval, 9.17-11.57), compared with 10.6 for people with MS without depression (95% CI, 9.99-11.21), 3.6 for people with depression but not MS (95% CI, 3.18-4.05), and 2.5 for people with neither condition (95% CI, 2.42-2.64). Compared with controls without depression, the 10-year hazard of all-cause mortality was increasingly greater in controls with depression (hazard ratio, 1.75; 95% CI, 1.59-1.91), people with MS but not depression (HR, 3.88; 95% CI, 3.66-4.10), and people with MS and depression (HR, 5.43; 95% CI, 4.88-5.96). Overall, 14% of the observed effect on mortality was attributable to the interaction between MS status and depression.

As for vascular diseases, people with MS had an increased risk regardless of their depression status. That said, people with MS and depression (HR, 3.30; 95% CI, 2.37-4.23) had a notably higher risk than people with MS and no depression (HR, 1.48; 95% CI, 1.23-1.74). Women with MS and depression also had a greater risk of vascular disease than women with MS and no depression, while men with MS did not have significantly different risks of acute coronary syndrome or composite macrovascular disease than those in the control group who did not suffer from depression.
 

Does treating depression decrease the likelihood of vascular disease?

“The take-home message for me is the importance of treating depression in this population, in which we see it with great regularity,” Joseph Berger, MD, professor of neurology and associate chief of the multiple sclerosis division at the University of Pennsylvania, Philadelphia, said in an interview. “The question that I have is: If you treat depression in an individual with MS or an individual who is simply depressed and thus at risk for the subsequent development of vascular disease, does it decrease the likelihood of their subsequent development of vascular disease in comparison to had you not?

“I presume it does,” he added, noting that “the theories underlying why depression would increase one’s risk of subsequent vascular disease are enumerated by the authors, including such things as increased inflammation. Now, the inflammation may be contributing to the depression, or the depression may be contributing to the inflammation; it may be one of those chicken-and-egg scenarios. But if you decrease the depression, do you thereby decrease the inflammation, which has a pernicious effect on endothelial cells and increases one’s vascular risk?

“Alternatively, lifestyle in depressed patients is also altered,” he said. “They’re far less likely to engage in exercise, healthy habits, and healthy diets, and more likely perhaps to smoke. These all need to be addressed, but this study certainly gives you a greater impetus as a MS neurologist to address the issue of depression, realizing that there is also this comorbidity of vascular disease.”
 

Evaluating the biological interaction between MS and depression

Based on this and other studies, the joint effect of MS and depression on all-cause mortality may qualify as a biological interaction, Amber Salter, PhD, of the University of Texas Southwestern Medical Center, Dallas, wrote in an accompanying editorial.

“Biological interactions consider whether the joint effect of two factors follow an additive pattern, or the joint effect of two factors is greater than the sum of the individual effects for each factor alone,” she wrote. And though the interaction was not found to be present for vascular disease and cardiovascular mortality, it was for all-cause mortality.

“When warranted, the evaluation of biological interactions in future studies should be considered to provide insight on target subpopulations for interventions or test for potential mechanistic forms of interaction,” she added.

Dr. Salter highlighted the study’s strengths, including a large sample size and six controls matched to each MS patient. She also stated that the researchers’ inability to control for risk factors like body mass index and physical activity means the 14% increase in mortality “may not be a large absolute increase in mortality when other covariates cannot be considered.” In addition, their lack of data on suicide – and its association with depression – offers up the possibility that increases in mortality could be tied to a “potentially modifiable risk” as opposed to a biologically increased one.

In acknowledging their study’s limitations, the authors stated that body mass index, though an important vascular risk factor, has a “modest” association with mortality, and that the average annual suicide rate in the MS population – though higher than in the non-MS population – is still “relatively low.”

Two of the authors disclosed receiving support, including grants and research funding, from various institutions and organizations in the United Kingdom, the United States, and Canada, as well as several pharmaceutical companies. Dr. Salter reported no relevant disclosures.

People with multiple sclerosis (MS) and depression have an increased risk of death, compared with those with one or neither condition, as well as an increased risk of vascular disease, a new study has found. “The effects of depression and MS on all-cause mortality are synergistic,” wrote lead author Raffaele Palladino, MD, PhD, research associate, faculty of medicine, Imperial College London.

The study was published in Neurology.

To assess the association between depression, vascular disease, and death in patients with MS, the researchers launched a population-based retrospective cohort study that reviewed English medical records from January 1987 to December 2018 and matched people with and without MS. Ultimately, 12,251 people with MS were matched with 72,572 controls. At baseline, 21% of the MS group (n = 2,535) and 9% of the controls (n = 6,278) had depression. Women were the majority in both cohorts and were more likely than men to be depressed.

People with both MS and depression had an all-cause mortality rate of 10.3 cases per 100,000 person-years (95% confidence interval, 9.17-11.57), compared with 10.6 for people with MS without depression (95% CI, 9.99-11.21), 3.6 for people with depression but not MS (95% CI, 3.18-4.05), and 2.5 for people with neither condition (95% CI, 2.42-2.64). Compared with controls without depression, the 10-year hazard of all-cause mortality was increasingly greater in controls with depression (hazard ratio, 1.75; 95% CI, 1.59-1.91), people with MS but not depression (HR, 3.88; 95% CI, 3.66-4.10), and people with MS and depression (HR, 5.43; 95% CI, 4.88-5.96). Overall, 14% of the observed effect on mortality was attributable to the interaction between MS status and depression.

As for vascular diseases, people with MS had an increased risk regardless of their depression status. That said, people with MS and depression (HR, 3.30; 95% CI, 2.37-4.23) had a notably higher risk than people with MS and no depression (HR, 1.48; 95% CI, 1.23-1.74). Women with MS and depression also had a greater risk of vascular disease than women with MS and no depression, while men with MS did not have significantly different risks of acute coronary syndrome or composite macrovascular disease than those in the control group who did not suffer from depression.
 

Does treating depression decrease the likelihood of vascular disease?

“The take-home message for me is the importance of treating depression in this population, in which we see it with great regularity,” Joseph Berger, MD, professor of neurology and associate chief of the multiple sclerosis division at the University of Pennsylvania, Philadelphia, said in an interview. “The question that I have is: If you treat depression in an individual with MS or an individual who is simply depressed and thus at risk for the subsequent development of vascular disease, does it decrease the likelihood of their subsequent development of vascular disease in comparison to had you not?

“I presume it does,” he added, noting that “the theories underlying why depression would increase one’s risk of subsequent vascular disease are enumerated by the authors, including such things as increased inflammation. Now, the inflammation may be contributing to the depression, or the depression may be contributing to the inflammation; it may be one of those chicken-and-egg scenarios. But if you decrease the depression, do you thereby decrease the inflammation, which has a pernicious effect on endothelial cells and increases one’s vascular risk?

“Alternatively, lifestyle in depressed patients is also altered,” he said. “They’re far less likely to engage in exercise, healthy habits, and healthy diets, and more likely perhaps to smoke. These all need to be addressed, but this study certainly gives you a greater impetus as a MS neurologist to address the issue of depression, realizing that there is also this comorbidity of vascular disease.”
 

Evaluating the biological interaction between MS and depression

Based on this and other studies, the joint effect of MS and depression on all-cause mortality may qualify as a biological interaction, Amber Salter, PhD, of the University of Texas Southwestern Medical Center, Dallas, wrote in an accompanying editorial.

“Biological interactions consider whether the joint effect of two factors follow an additive pattern, or the joint effect of two factors is greater than the sum of the individual effects for each factor alone,” she wrote. And though the interaction was not found to be present for vascular disease and cardiovascular mortality, it was for all-cause mortality.

“When warranted, the evaluation of biological interactions in future studies should be considered to provide insight on target subpopulations for interventions or test for potential mechanistic forms of interaction,” she added.

Dr. Salter highlighted the study’s strengths, including a large sample size and six controls matched to each MS patient. She also stated that the researchers’ inability to control for risk factors like body mass index and physical activity means the 14% increase in mortality “may not be a large absolute increase in mortality when other covariates cannot be considered.” In addition, their lack of data on suicide – and its association with depression – offers up the possibility that increases in mortality could be tied to a “potentially modifiable risk” as opposed to a biologically increased one.

In acknowledging their study’s limitations, the authors stated that body mass index, though an important vascular risk factor, has a “modest” association with mortality, and that the average annual suicide rate in the MS population – though higher than in the non-MS population – is still “relatively low.”

Two of the authors disclosed receiving support, including grants and research funding, from various institutions and organizations in the United Kingdom, the United States, and Canada, as well as several pharmaceutical companies. Dr. Salter reported no relevant disclosures.

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Emerging evidence suggests that autoimmunity plays a role in postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that targeting autoantibodies could be a promising treatment approach.

The same may also apply to many cases of “long COVID,” in which many of the symptoms overlap with those of ME/CFS, Carmen Scheibenbogen, MD, professor of clinical immunology and director of the Institute for Medical Immunology, Charité University Medicine, Berlin, said during the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Several groups, including Dr. Scheibenbogen’s, have reported finding autoantibodies against neurotransmitter receptor antigens in people with ME/CFS. And, in a paper published in the Journal of Clinical Medicine the day that Dr. Scheibenbogen spoke at the meeting, her team reported significant correlations between autoantibodies to vasoregulative G-protein–coupled receptors and symptom severity, autonomic dysfunction, and disability among 116 patients with infection-triggered ME/CFS who were diagnosed using the symptom-based 2003 Canadian consensus criteria.

People with ME/CFS are also more likely to have genetic risk factors associated with autoimmunity and personal and/or family histories of autoimmune conditions. And, clinical trials have demonstrated early success with various immunomodulatory treatments in subsets of people with ME/CFS, including endoxan, rituximab, and immunoadsorption.

“We have evidence that ME/CFS is an autoantibody-mediated disease, and we have evidence that autoantibody targeting is effective in this disease. So far ... we have few and underfinanced clinical studies, but the good news is we have promising emerging treatment options,” Dr. Scheibenbogen said.

Asked to comment, ME/CFS expert Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said: “There is already strong evidence that there are autoantibodies in ME/CFS. Dr. Scheibenbogen’s work is the latest and employs the latest technology. ... I would bet that autoantibodies to neural targets are likely to cause some of the symptoms of ME/CFS and some of the symptoms of long COVID.”

However, he cautioned, “that has not been proven, and even if it were proven you would have to demonstrate that treatments based on that theory worked.”

Dr. Komaroff said he views autoimmunity as a likely component of the ME/CFS spectrum, but not the only one. “My current view of this illness is that there’s a final common pathway in the brain that leads to the symptoms of the illness. But that final common pathway can be triggered by a variety of different things, one of which could be autoantibodies while another could be infection or inflammation in the brain.”
 

Emerging evidence points to autoimmunity

Dr. Scheibenbogen summarized the work published in this area over the past few years by her group and others.

In a comparison of ME/CFS patients with 201 healthy controls, significant associations were seen with two specific autoimmunity-related risk alleles only in the ME/CFS patients who reported acute onset of disease with an infection but not in those with ME/CFS without infection-triggered onset or the controls. Both genes play roles in regulating B- and T-cell activation.

Another recent study found associations with ME/CFS and major histocompatibility complex class II molecules, a typical feature of autoimmune diseases, in a comparison between 426 adult Norwegian ME/CFS patients who were diagnosed with the Canadian consensus criteria and 4,511 healthy, ethnically matched controls.

In a 2020 paper, Dr. Scheibenbogen and pharmacologist Klaus Wirth presented a “unifying hypothesis” of ME/CFS pathophysiology based on the finding of elevations in autoantibodies against beta₂-adrenergic receptors and muscarinic acetylcholine receptors in some individuals with the condition. Since both of those receptors are important vasodilators, their functional disturbance would be expected to cause vasoconstriction and hypoxemia, which would explain many of the symptoms of ME/CFS. This mechanism would align with other findings of muscular and cerebral hypoperfusion that correlate with fatigue, particularly post exertion, as well as metabolic changes that are in line with the concepts of hypoxemia and ischemia.

Further evidence for vascular dysfunction in ME/CFS came from her group’s study finding evidence of peripheral endothelial dysfunction that was associated with symptom severity in 35 adult patients. “Vasoconstriction, hypovolemia, and release of vasoactive and algesic mediators is probably a key pathomechanism of the disease,” Dr. Scheibenbogen said.
 

Treatments: Will targeting autoantibodies work?

In the second part of her talk, Dr. Scheibenbogen summarized clinical trials of the following treatment approaches that involve targeting autoantibodies as a way to alleviate ME/CFS symptoms:

Rituximab: Work on infusions of the B-cell depleting agent has been conducted by Norwegian researchers beginning in 2011 with a small randomized trial and an open-label, phase 2 study in 2015, both showing clinical responses in ME/CFS. However, a subsequent phase 3, randomized clinical trial of 151 patients, again diagnosed using the Canadian criteria, was negative.

There are several possible explanations for this, Dr. Scheibenbogen noted. For one, the maintenance dose had to be reduced because of a lack of financial support. “This was probably critical. The lower dose was insufficient to adequately deplete B cells.” Also, there may have been a strong placebo response in the control group since they were being given better care than they normally would receive during the trial. “I think probably nobody will again do a rituximab trial. This was very disappointing for all of us. But, we still have other opportunities to follow this path,” she said.

Dr. Komaroff agreed. “I don’t think the failure of one drug that hits malignant B cells is proof against the autoimmune hypothesis per se. I think the evidence is that rituximab doesn’t work, but that doesn’t invalidate the autoimmunity hypothesis.”

Cyclophosphamide: The same Norwegian group also showed positive findings in an open-label, phase 2 trial of the immune-modifying drug cyclophosphamide in 22 of 40 patients. Interestingly, HLA risk alleles were much more common in responders than nonresponders, Dr. Scheibenbogen noted.

Immunoadsorption: This technique, similar to dialysis, involves separating out the blood plasma by centrifugation and removing IgG autoantibodies by a binding column, then returning the plasma back to the patient. It is used, primarily in Europe, to treat severe autoimmune diseases including dilative cardiomyopathy and refractory systemic lupus erythematosus (SLE).

Dr. Scheibenbogen’s group has conducted two studies of immunoadsorption in ME/CFS. In one, a 5-day procedure led to rapid symptom improvement in 7 of 10 patients, with sustained improvement in 3 patients after 2 years. Autoantibodies decreased rapidly in 9 of the 10 patients. In a follow-up study of five of the responders 2 years later, retreatment with a modified immunoadsorption protocol led to rapid and sustained improvement in four. Further study has been on hold because of the pandemic.

Next-gen IgG-targeting therapies: Another approach that could offer promise for ME/CFS involves therapies that block the Fc receptors of IgG. Several are in phase 1-3 trials for autoimmune conditions. One candidate drug, the Fc fragment efgartigimod, is currently in phase 3 trials for several conditions, including generalized myasthenia gravis, primary immune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy. Phase 3 trials are planned for the monoclonal antibody rozanolixizumab in those same conditions.

Newer-generation monoclonal antibodies targeting CD19 or CD20 that show benefit in various autoimmune conditions are another possibility for ME/CFS. These include ocrelizumab (Ocrevus), approved in the United States for treating relapsing and progressive multiple sclerosis and in trials for SLE; obinutuzumab (Gazyva), approved for treating lymphoma and also in development for SLE; and ublituximab, in phase 3 trials for multiple sclerosis.

“Most of them are more effective than rituximab,” Dr. Scheibenbogen noted, adding that “currently the data look quite promising. They are effective in different autoimmune diseases and they are quite well tolerated. There’s great hope now with COVID-19 that we can convince some companies to do such trials in ME/CFS as well.”

Dr. Scheibenbogen’s institution, the Charité Fatigue Center, has a patent for beta₂-adrenergic receptor antibodies for diagnosing ME/CFS under her name together with Celltrend. Dr. Komaroff has received personal fees from Serimmune.

Emerging evidence suggests that autoimmunity plays a role in postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that targeting autoantibodies could be a promising treatment approach.

The same may also apply to many cases of “long COVID,” in which many of the symptoms overlap with those of ME/CFS, Carmen Scheibenbogen, MD, professor of clinical immunology and director of the Institute for Medical Immunology, Charité University Medicine, Berlin, said during the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Several groups, including Dr. Scheibenbogen’s, have reported finding autoantibodies against neurotransmitter receptor antigens in people with ME/CFS. And, in a paper published in the Journal of Clinical Medicine the day that Dr. Scheibenbogen spoke at the meeting, her team reported significant correlations between autoantibodies to vasoregulative G-protein–coupled receptors and symptom severity, autonomic dysfunction, and disability among 116 patients with infection-triggered ME/CFS who were diagnosed using the symptom-based 2003 Canadian consensus criteria.

People with ME/CFS are also more likely to have genetic risk factors associated with autoimmunity and personal and/or family histories of autoimmune conditions. And, clinical trials have demonstrated early success with various immunomodulatory treatments in subsets of people with ME/CFS, including endoxan, rituximab, and immunoadsorption.

“We have evidence that ME/CFS is an autoantibody-mediated disease, and we have evidence that autoantibody targeting is effective in this disease. So far ... we have few and underfinanced clinical studies, but the good news is we have promising emerging treatment options,” Dr. Scheibenbogen said.

Asked to comment, ME/CFS expert Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said: “There is already strong evidence that there are autoantibodies in ME/CFS. Dr. Scheibenbogen’s work is the latest and employs the latest technology. ... I would bet that autoantibodies to neural targets are likely to cause some of the symptoms of ME/CFS and some of the symptoms of long COVID.”

However, he cautioned, “that has not been proven, and even if it were proven you would have to demonstrate that treatments based on that theory worked.”

Dr. Komaroff said he views autoimmunity as a likely component of the ME/CFS spectrum, but not the only one. “My current view of this illness is that there’s a final common pathway in the brain that leads to the symptoms of the illness. But that final common pathway can be triggered by a variety of different things, one of which could be autoantibodies while another could be infection or inflammation in the brain.”
 

Emerging evidence points to autoimmunity

Dr. Scheibenbogen summarized the work published in this area over the past few years by her group and others.

In a comparison of ME/CFS patients with 201 healthy controls, significant associations were seen with two specific autoimmunity-related risk alleles only in the ME/CFS patients who reported acute onset of disease with an infection but not in those with ME/CFS without infection-triggered onset or the controls. Both genes play roles in regulating B- and T-cell activation.

Another recent study found associations with ME/CFS and major histocompatibility complex class II molecules, a typical feature of autoimmune diseases, in a comparison between 426 adult Norwegian ME/CFS patients who were diagnosed with the Canadian consensus criteria and 4,511 healthy, ethnically matched controls.

In a 2020 paper, Dr. Scheibenbogen and pharmacologist Klaus Wirth presented a “unifying hypothesis” of ME/CFS pathophysiology based on the finding of elevations in autoantibodies against beta₂-adrenergic receptors and muscarinic acetylcholine receptors in some individuals with the condition. Since both of those receptors are important vasodilators, their functional disturbance would be expected to cause vasoconstriction and hypoxemia, which would explain many of the symptoms of ME/CFS. This mechanism would align with other findings of muscular and cerebral hypoperfusion that correlate with fatigue, particularly post exertion, as well as metabolic changes that are in line with the concepts of hypoxemia and ischemia.

Further evidence for vascular dysfunction in ME/CFS came from her group’s study finding evidence of peripheral endothelial dysfunction that was associated with symptom severity in 35 adult patients. “Vasoconstriction, hypovolemia, and release of vasoactive and algesic mediators is probably a key pathomechanism of the disease,” Dr. Scheibenbogen said.
 

Treatments: Will targeting autoantibodies work?

In the second part of her talk, Dr. Scheibenbogen summarized clinical trials of the following treatment approaches that involve targeting autoantibodies as a way to alleviate ME/CFS symptoms:

Rituximab: Work on infusions of the B-cell depleting agent has been conducted by Norwegian researchers beginning in 2011 with a small randomized trial and an open-label, phase 2 study in 2015, both showing clinical responses in ME/CFS. However, a subsequent phase 3, randomized clinical trial of 151 patients, again diagnosed using the Canadian criteria, was negative.

There are several possible explanations for this, Dr. Scheibenbogen noted. For one, the maintenance dose had to be reduced because of a lack of financial support. “This was probably critical. The lower dose was insufficient to adequately deplete B cells.” Also, there may have been a strong placebo response in the control group since they were being given better care than they normally would receive during the trial. “I think probably nobody will again do a rituximab trial. This was very disappointing for all of us. But, we still have other opportunities to follow this path,” she said.

Dr. Komaroff agreed. “I don’t think the failure of one drug that hits malignant B cells is proof against the autoimmune hypothesis per se. I think the evidence is that rituximab doesn’t work, but that doesn’t invalidate the autoimmunity hypothesis.”

Cyclophosphamide: The same Norwegian group also showed positive findings in an open-label, phase 2 trial of the immune-modifying drug cyclophosphamide in 22 of 40 patients. Interestingly, HLA risk alleles were much more common in responders than nonresponders, Dr. Scheibenbogen noted.

Immunoadsorption: This technique, similar to dialysis, involves separating out the blood plasma by centrifugation and removing IgG autoantibodies by a binding column, then returning the plasma back to the patient. It is used, primarily in Europe, to treat severe autoimmune diseases including dilative cardiomyopathy and refractory systemic lupus erythematosus (SLE).

Dr. Scheibenbogen’s group has conducted two studies of immunoadsorption in ME/CFS. In one, a 5-day procedure led to rapid symptom improvement in 7 of 10 patients, with sustained improvement in 3 patients after 2 years. Autoantibodies decreased rapidly in 9 of the 10 patients. In a follow-up study of five of the responders 2 years later, retreatment with a modified immunoadsorption protocol led to rapid and sustained improvement in four. Further study has been on hold because of the pandemic.

Next-gen IgG-targeting therapies: Another approach that could offer promise for ME/CFS involves therapies that block the Fc receptors of IgG. Several are in phase 1-3 trials for autoimmune conditions. One candidate drug, the Fc fragment efgartigimod, is currently in phase 3 trials for several conditions, including generalized myasthenia gravis, primary immune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy. Phase 3 trials are planned for the monoclonal antibody rozanolixizumab in those same conditions.

Newer-generation monoclonal antibodies targeting CD19 or CD20 that show benefit in various autoimmune conditions are another possibility for ME/CFS. These include ocrelizumab (Ocrevus), approved in the United States for treating relapsing and progressive multiple sclerosis and in trials for SLE; obinutuzumab (Gazyva), approved for treating lymphoma and also in development for SLE; and ublituximab, in phase 3 trials for multiple sclerosis.

“Most of them are more effective than rituximab,” Dr. Scheibenbogen noted, adding that “currently the data look quite promising. They are effective in different autoimmune diseases and they are quite well tolerated. There’s great hope now with COVID-19 that we can convince some companies to do such trials in ME/CFS as well.”

Dr. Scheibenbogen’s institution, the Charité Fatigue Center, has a patent for beta₂-adrenergic receptor antibodies for diagnosing ME/CFS under her name together with Celltrend. Dr. Komaroff has received personal fees from Serimmune.

Emerging evidence suggests that autoimmunity plays a role in postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that targeting autoantibodies could be a promising treatment approach.

The same may also apply to many cases of “long COVID,” in which many of the symptoms overlap with those of ME/CFS, Carmen Scheibenbogen, MD, professor of clinical immunology and director of the Institute for Medical Immunology, Charité University Medicine, Berlin, said during the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Several groups, including Dr. Scheibenbogen’s, have reported finding autoantibodies against neurotransmitter receptor antigens in people with ME/CFS. And, in a paper published in the Journal of Clinical Medicine the day that Dr. Scheibenbogen spoke at the meeting, her team reported significant correlations between autoantibodies to vasoregulative G-protein–coupled receptors and symptom severity, autonomic dysfunction, and disability among 116 patients with infection-triggered ME/CFS who were diagnosed using the symptom-based 2003 Canadian consensus criteria.

People with ME/CFS are also more likely to have genetic risk factors associated with autoimmunity and personal and/or family histories of autoimmune conditions. And, clinical trials have demonstrated early success with various immunomodulatory treatments in subsets of people with ME/CFS, including endoxan, rituximab, and immunoadsorption.

“We have evidence that ME/CFS is an autoantibody-mediated disease, and we have evidence that autoantibody targeting is effective in this disease. So far ... we have few and underfinanced clinical studies, but the good news is we have promising emerging treatment options,” Dr. Scheibenbogen said.

Asked to comment, ME/CFS expert Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said: “There is already strong evidence that there are autoantibodies in ME/CFS. Dr. Scheibenbogen’s work is the latest and employs the latest technology. ... I would bet that autoantibodies to neural targets are likely to cause some of the symptoms of ME/CFS and some of the symptoms of long COVID.”

However, he cautioned, “that has not been proven, and even if it were proven you would have to demonstrate that treatments based on that theory worked.”

Dr. Komaroff said he views autoimmunity as a likely component of the ME/CFS spectrum, but not the only one. “My current view of this illness is that there’s a final common pathway in the brain that leads to the symptoms of the illness. But that final common pathway can be triggered by a variety of different things, one of which could be autoantibodies while another could be infection or inflammation in the brain.”
 

Emerging evidence points to autoimmunity

Dr. Scheibenbogen summarized the work published in this area over the past few years by her group and others.

In a comparison of ME/CFS patients with 201 healthy controls, significant associations were seen with two specific autoimmunity-related risk alleles only in the ME/CFS patients who reported acute onset of disease with an infection but not in those with ME/CFS without infection-triggered onset or the controls. Both genes play roles in regulating B- and T-cell activation.

Another recent study found associations with ME/CFS and major histocompatibility complex class II molecules, a typical feature of autoimmune diseases, in a comparison between 426 adult Norwegian ME/CFS patients who were diagnosed with the Canadian consensus criteria and 4,511 healthy, ethnically matched controls.

In a 2020 paper, Dr. Scheibenbogen and pharmacologist Klaus Wirth presented a “unifying hypothesis” of ME/CFS pathophysiology based on the finding of elevations in autoantibodies against beta₂-adrenergic receptors and muscarinic acetylcholine receptors in some individuals with the condition. Since both of those receptors are important vasodilators, their functional disturbance would be expected to cause vasoconstriction and hypoxemia, which would explain many of the symptoms of ME/CFS. This mechanism would align with other findings of muscular and cerebral hypoperfusion that correlate with fatigue, particularly post exertion, as well as metabolic changes that are in line with the concepts of hypoxemia and ischemia.

Further evidence for vascular dysfunction in ME/CFS came from her group’s study finding evidence of peripheral endothelial dysfunction that was associated with symptom severity in 35 adult patients. “Vasoconstriction, hypovolemia, and release of vasoactive and algesic mediators is probably a key pathomechanism of the disease,” Dr. Scheibenbogen said.
 

Treatments: Will targeting autoantibodies work?

In the second part of her talk, Dr. Scheibenbogen summarized clinical trials of the following treatment approaches that involve targeting autoantibodies as a way to alleviate ME/CFS symptoms:

Rituximab: Work on infusions of the B-cell depleting agent has been conducted by Norwegian researchers beginning in 2011 with a small randomized trial and an open-label, phase 2 study in 2015, both showing clinical responses in ME/CFS. However, a subsequent phase 3, randomized clinical trial of 151 patients, again diagnosed using the Canadian criteria, was negative.

There are several possible explanations for this, Dr. Scheibenbogen noted. For one, the maintenance dose had to be reduced because of a lack of financial support. “This was probably critical. The lower dose was insufficient to adequately deplete B cells.” Also, there may have been a strong placebo response in the control group since they were being given better care than they normally would receive during the trial. “I think probably nobody will again do a rituximab trial. This was very disappointing for all of us. But, we still have other opportunities to follow this path,” she said.

Dr. Komaroff agreed. “I don’t think the failure of one drug that hits malignant B cells is proof against the autoimmune hypothesis per se. I think the evidence is that rituximab doesn’t work, but that doesn’t invalidate the autoimmunity hypothesis.”

Cyclophosphamide: The same Norwegian group also showed positive findings in an open-label, phase 2 trial of the immune-modifying drug cyclophosphamide in 22 of 40 patients. Interestingly, HLA risk alleles were much more common in responders than nonresponders, Dr. Scheibenbogen noted.

Immunoadsorption: This technique, similar to dialysis, involves separating out the blood plasma by centrifugation and removing IgG autoantibodies by a binding column, then returning the plasma back to the patient. It is used, primarily in Europe, to treat severe autoimmune diseases including dilative cardiomyopathy and refractory systemic lupus erythematosus (SLE).

Dr. Scheibenbogen’s group has conducted two studies of immunoadsorption in ME/CFS. In one, a 5-day procedure led to rapid symptom improvement in 7 of 10 patients, with sustained improvement in 3 patients after 2 years. Autoantibodies decreased rapidly in 9 of the 10 patients. In a follow-up study of five of the responders 2 years later, retreatment with a modified immunoadsorption protocol led to rapid and sustained improvement in four. Further study has been on hold because of the pandemic.

Next-gen IgG-targeting therapies: Another approach that could offer promise for ME/CFS involves therapies that block the Fc receptors of IgG. Several are in phase 1-3 trials for autoimmune conditions. One candidate drug, the Fc fragment efgartigimod, is currently in phase 3 trials for several conditions, including generalized myasthenia gravis, primary immune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy. Phase 3 trials are planned for the monoclonal antibody rozanolixizumab in those same conditions.

Newer-generation monoclonal antibodies targeting CD19 or CD20 that show benefit in various autoimmune conditions are another possibility for ME/CFS. These include ocrelizumab (Ocrevus), approved in the United States for treating relapsing and progressive multiple sclerosis and in trials for SLE; obinutuzumab (Gazyva), approved for treating lymphoma and also in development for SLE; and ublituximab, in phase 3 trials for multiple sclerosis.

“Most of them are more effective than rituximab,” Dr. Scheibenbogen noted, adding that “currently the data look quite promising. They are effective in different autoimmune diseases and they are quite well tolerated. There’s great hope now with COVID-19 that we can convince some companies to do such trials in ME/CFS as well.”

Dr. Scheibenbogen’s institution, the Charité Fatigue Center, has a patent for beta₂-adrenergic receptor antibodies for diagnosing ME/CFS under her name together with Celltrend. Dr. Komaroff has received personal fees from Serimmune.

The evolution of illness prevention, diagnosis, and treatment has involved an increased appreciation for the clinical utility of longitudinal assessment. This has included the implementation of screening evaluations for high base rate medical conditions, such as cancer, that involve considerable morbidity and mortality.

Unfortunately, the mental health professions have been slow to embrace this approach. Baseline assessment with psychological/neuropsychological screening tests and more comprehensive test batteries to clarify diagnostic status and facilitate treatment planning is far more the exception than the rule in mental health care. This seems to be the case despite the strong evidence supporting this practice as well as multiple surveys indicating that psychiatrists and other physicians report a high level of satisfaction with the findings and recommendations of psychological/neuropsychological test reports.^1-3

There is a substantial literature that reviews the relative indications and contraindications for initial psychological/neuropsychological test evaluations.^4-7 However, there is a paucity of clinical and evidence-based information regarding criteria for follow-up assessment. Moreover, there are no consensus guidelines to inform decision-making regarding this issue.

In general, good clinical practice for baseline assessment and reexamination should include administration of both psychological and neuropsychological tests. Based on clinical experience, this article addresses the relative indications and contraindications for psychological/neuropsychological test reassessment of adults seen in psychiatric care. It also outlines suggested time frames for such reevaluations, based on the patient’s clinical status and circumstances.

Why are patients not referred for reassessment more often?

There are several reasons patients are not referred for follow-up testing, beginning with the failure, at times, of the psychologist to state in the recommendations section of the test report whether a reassessment is indicated, under what circumstances, and within what time frame. Empirical data is lacking, but predicated on clinical experience, even when a strong and unequivocal recommendation is made for reassessment, only a very small percentage of patients are seen for follow-up evaluation.

There are numerous reasons why this occurs. The patient and/or the psychiatrist may overlook or forget about the recommendation for reassessment, particularly if it was embedded in a lengthy list of recommendations and the suggested time frame for the reassessment was several years away. The patient and the psychiatrist may decide against going forward with a reexamination, for a variety of substantive reasons. The patient might decline, against medical advice, to be retested. The patient may fail to make or keep an appointment for the follow-up reexamination. The patient might leave treatment and become lost to follow-up. The patient might not be able to find an appropriate psychologist. The insurance company may decline to authorize follow-up testing.⁸

Indications for reevaluation

Follow-up testing generally is indicated in the following circumstances:

Patients who are likely to soon improve or worsen. Reassessment is indicated when, based on the initial evaluation, the patient has been identified as having a neuropsychiatric disorder that is likely to improve or worsen over the next year or 2 due to the natural trajectory of the condition and the degree to which it may respond to treatment.

Continue to: Patients who are likely...

Patients who are likely to improve include those with mental status changes referable to ≥1 medical and/or neuropsychiatric factors that are considered at least partially treatable and reversible. Patients who fall within this category include those who have mild to moderately severe head trauma or stroke, have a suspected or known medication- or substance-induced altered mental status, appear to have depression-related cognitive difficulties, or have an initial or recurrent episode of idiopathic psychosis.

Patients whose conditions can be expected to worsen over time include those with a mild neurocognitive disorder or major neuro­cognitive disorder of mild severity that is considered referable to a progressive neurodegenerative illness such as Alzheimer’s disease based on family and personal history, their psychometric test profile, and other factors, including findings from positron emission tomography scanning.

Older patients who were referred primarily due to a strong family history of major neurocognitive disorder but with no clear-cut concerning findings on baseline testing warrant reevaluation in the event of the emergence of significant cognitive and/or psychiatric symptoms and/or a functional decline since the baseline examination.

Patients who have been seen for initial test evaluations prior to interventions such as neuro­surgery (including psychosurgery), electroconvulsive therapy (ECT), transcranial magnetic stimulation, cognitive rehabilitation, etc.

Patients undergoing a substantial transition. Reevaluation is appropriate for a broad range of patients experiencing difficulties when undergoing a significant lifestyle transition or change in level of care. This includes patients considering a return to school or work after a prolonged absence due to neuropsychiatric illness, or for whom there are questions regarding the need for a change in their level of everyday care. The latter includes patients who are returning to home care from assisted living, or transferring from home-based services to assisted living or a skilled nursing facility.

Continue to: What about patients with psychiatric disorders?

What about patients with psychiatric disorders? A “grey area” pertains to reassessment of patients with neuropsychiatric disorders such as schizophrenia and related psychotic disorders, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Patients with these conditions often have high rates of cognitive/neuropsychological impairment on baseline testing, even when they appear to be improving from a psychiatric perspective, are reasonably stable, and may even be in remission.^9-12

These deficits are frequently a mix of pre-illness, prodromal, and early-stage illness– related neurocognitive difficulties that, for the most part, remain stable over time. That said, there is emerging evidence of worsening cognitive change over time following a first episode of psychosis for some patients with schizophrenia.¹³

In general, reevaluation should be considered for patients with a family and/or personal history of cognitive/neuropsychological impairment, structural brain abnormalities on neuroimaging, a concerning cognitive/neuropsychological profile, or any other factors that raise the index of suspicion for a possible progressive deteriorative course of illness.^13,14

Patients with personality disorders who have had a baseline psychometric evaluation do not clearly warrant reassessment unless they develop medical and/or psychosocial difficulties that are often linked to problematic personality traits/patterns and that result in significant and persistent mental status changes. For example, reassessment might be indicated for a patient with borderline personality disorder who has new-onset or worsening cognitive and/or psychiatric complaints/symptoms after sustaining a head injury while intoxicated and embroiled in a domestic conflict triggered by anger and fears related to abandonment and separation.

Reevaluation also should be considered when a patient with a personality disorder has had a baseline assessment and subsequently completes an intensive, long-term treatment program that is likely to improve their clinical status. In this context, retesting may help document these gains. Examples of such programs/services include residential psychiatric and/or substance abuse care, object relational/psychodynamically-based psychotherapy, an extended course of dialectical behavioral therapy, or a related coping skills/distress tolerance psychotherapy.

Continue to: Contraindications for reassessment

Contraindications for reassessment

Retesting generally is not indicated in the following circumstances:

Patients with advanced major neurocognitive disorder. Reassessment is not indicated for such patients when there are no new questions regarding diagnosis, prognosis, level of care, and/or related disposition issues.

Patients with transient episodes of poor functioning. For the most part, reassessment is not helpful for patients with well-established diagnoses and treatment plans who, based on their history, experience time-limited, recurrent episodes of poor functioning and then reliably return to their baseline with ongoing psychiatric care. This includes patients with borderline personality disorder and other personality difficulties with histories of transient decompensation in response to psychosocial and psychodynamic triggers.

Patients who do not improve or worsen over time. Reassessment is not indicated when there has been no clear, sustained improvement or worsening of a patient’s clinical status over an extended time, and a protracted change is not anticipated. In this situation, reassessment is unlikely to yield clinically useful information beyond what is already known or meaningfully impact case formulation and treatment planning.

The Table^9-14 summarizes the relative indications and contraindications for psychological/neuropsychological reexamination.

Continue to: Time frames for reassessment

 

 

Time frames for reassessment

Time frames for retesting vary considerably depending on factors such as diagnostic status, longitudinal course, treatment parameters, and recent/current life circumstances.

While empirical data is lacking regarding this matter, based on clinical experience, reevaluation in 18 to 24 months is generally appropriate for patients with neuro­psychiatric conditions who are likely to gradually improve or slowly worsen over this time. Still, reexamination can be sooner (within 12 to 18 months) for patients who have experienced a more rapid and steep negative change in clinical status than initially anticipated.

For most patients with major mental illness, reexamination in 3 to 5 years is probably a reasonable time interval, barring a poorly understood and clinically significant negative change in functioning that warrants a shorter time frame. This suggested time frame would allow for sufficient time to better gauge improvement, stability, or deterioration in functioning and whether the reason(s) for referral have evolved. On the other hand, this time interval is somewhat arbitrary given the lack of empirical data. Therefore, on a case-by-case basis, it would be helpful for psychiatrists to consult with their patients and preferably with the psychologist who completed the baseline evaluation to determine a reasonable interval between assessments.

For patients who have undergone long-term/intensive treatment, reassessment in 3 or 6 months to as long as 1 year after the patient completes the program should be considered. Patients who undergo medical interventions such as neurosurgery or ECT—which can be associated with short-term, at least partially reversible negative effects on mental status—reassessment usually is most helpful when initiated as one or more screening level examinations for several weeks, followed by a comprehensive psychometric reassessment at the 3- to 6-month mark.

Suggestions for future research

Additional research is needed to ascertain the attitudes and opinions of psychiatrists and other physicians who use psychometric test data regarding how psychologists can most effectively communicate a recommendation for reassessment in their reports and clarify the ways psychiatrists can productively address this issue with their patients. Survey research of this kind should include questions about the frequency with which psychiatrists formally refer patients for retesting, and estimates of the rate of follow-through.

Continue to: It also would be desirable...

It also would be desirable to investigate factors that may facilitate follow-through with recommendations for reassessment, or, conversely, identify reasons that psychiatrists and their patients may decide to forgo reassessment. It would be important to try to obtain information regarding the optimum time frames for such reevaluation, depending on the patient’s circumstances and other variables. Evidence-based data pertaining to these issues would contribute to the development of consensus guidelines and a standard of care for psychological/neuropsychological test reevaluation.

Bottom Line

Only a very small percentage of patients referred for follow-up psychological/ neuropsychological test reevaluation actually undergo reexamination. Such retesting may be most helpful for certain patient populations, such as those who are likely to soon improve or worsen, were referred based on a family history of major cognitive disorder but have no concerning findings on baseline testing, or are undergoing a substantial life transition.

Related Resources

• Thom R, Farrell HM. Neuroimaging in psychiatry: potentials and pitfalls. Current Psychiatry. 2019;18(12):27-28;33-34.
• Papakostas GI. Cognitive symptoms in patients with major depressive disorder and their implications for clinical practice. J Clin Psychiatry. 2014;75(1):8-14.
• American Board of Professional Neuropsychology. https://abn-board.com

The evolution of illness prevention, diagnosis, and treatment has involved an increased appreciation for the clinical utility of longitudinal assessment. This has included the implementation of screening evaluations for high base rate medical conditions, such as cancer, that involve considerable morbidity and mortality.

Unfortunately, the mental health professions have been slow to embrace this approach. Baseline assessment with psychological/neuropsychological screening tests and more comprehensive test batteries to clarify diagnostic status and facilitate treatment planning is far more the exception than the rule in mental health care. This seems to be the case despite the strong evidence supporting this practice as well as multiple surveys indicating that psychiatrists and other physicians report a high level of satisfaction with the findings and recommendations of psychological/neuropsychological test reports.^1-3

There is a substantial literature that reviews the relative indications and contraindications for initial psychological/neuropsychological test evaluations.^4-7 However, there is a paucity of clinical and evidence-based information regarding criteria for follow-up assessment. Moreover, there are no consensus guidelines to inform decision-making regarding this issue.

In general, good clinical practice for baseline assessment and reexamination should include administration of both psychological and neuropsychological tests. Based on clinical experience, this article addresses the relative indications and contraindications for psychological/neuropsychological test reassessment of adults seen in psychiatric care. It also outlines suggested time frames for such reevaluations, based on the patient’s clinical status and circumstances.

Why are patients not referred for reassessment more often?

There are several reasons patients are not referred for follow-up testing, beginning with the failure, at times, of the psychologist to state in the recommendations section of the test report whether a reassessment is indicated, under what circumstances, and within what time frame. Empirical data is lacking, but predicated on clinical experience, even when a strong and unequivocal recommendation is made for reassessment, only a very small percentage of patients are seen for follow-up evaluation.

There are numerous reasons why this occurs. The patient and/or the psychiatrist may overlook or forget about the recommendation for reassessment, particularly if it was embedded in a lengthy list of recommendations and the suggested time frame for the reassessment was several years away. The patient and the psychiatrist may decide against going forward with a reexamination, for a variety of substantive reasons. The patient might decline, against medical advice, to be retested. The patient may fail to make or keep an appointment for the follow-up reexamination. The patient might leave treatment and become lost to follow-up. The patient might not be able to find an appropriate psychologist. The insurance company may decline to authorize follow-up testing.⁸

Indications for reevaluation

Follow-up testing generally is indicated in the following circumstances:

Patients who are likely to soon improve or worsen. Reassessment is indicated when, based on the initial evaluation, the patient has been identified as having a neuropsychiatric disorder that is likely to improve or worsen over the next year or 2 due to the natural trajectory of the condition and the degree to which it may respond to treatment.

Continue to: Patients who are likely...

Patients who are likely to improve include those with mental status changes referable to ≥1 medical and/or neuropsychiatric factors that are considered at least partially treatable and reversible. Patients who fall within this category include those who have mild to moderately severe head trauma or stroke, have a suspected or known medication- or substance-induced altered mental status, appear to have depression-related cognitive difficulties, or have an initial or recurrent episode of idiopathic psychosis.

Patients whose conditions can be expected to worsen over time include those with a mild neurocognitive disorder or major neuro­cognitive disorder of mild severity that is considered referable to a progressive neurodegenerative illness such as Alzheimer’s disease based on family and personal history, their psychometric test profile, and other factors, including findings from positron emission tomography scanning.

Older patients who were referred primarily due to a strong family history of major neurocognitive disorder but with no clear-cut concerning findings on baseline testing warrant reevaluation in the event of the emergence of significant cognitive and/or psychiatric symptoms and/or a functional decline since the baseline examination.

Patients who have been seen for initial test evaluations prior to interventions such as neuro­surgery (including psychosurgery), electroconvulsive therapy (ECT), transcranial magnetic stimulation, cognitive rehabilitation, etc.

Patients undergoing a substantial transition. Reevaluation is appropriate for a broad range of patients experiencing difficulties when undergoing a significant lifestyle transition or change in level of care. This includes patients considering a return to school or work after a prolonged absence due to neuropsychiatric illness, or for whom there are questions regarding the need for a change in their level of everyday care. The latter includes patients who are returning to home care from assisted living, or transferring from home-based services to assisted living or a skilled nursing facility.

Continue to: What about patients with psychiatric disorders?

What about patients with psychiatric disorders? A “grey area” pertains to reassessment of patients with neuropsychiatric disorders such as schizophrenia and related psychotic disorders, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Patients with these conditions often have high rates of cognitive/neuropsychological impairment on baseline testing, even when they appear to be improving from a psychiatric perspective, are reasonably stable, and may even be in remission.^9-12

These deficits are frequently a mix of pre-illness, prodromal, and early-stage illness– related neurocognitive difficulties that, for the most part, remain stable over time. That said, there is emerging evidence of worsening cognitive change over time following a first episode of psychosis for some patients with schizophrenia.¹³

In general, reevaluation should be considered for patients with a family and/or personal history of cognitive/neuropsychological impairment, structural brain abnormalities on neuroimaging, a concerning cognitive/neuropsychological profile, or any other factors that raise the index of suspicion for a possible progressive deteriorative course of illness.^13,14

Patients with personality disorders who have had a baseline psychometric evaluation do not clearly warrant reassessment unless they develop medical and/or psychosocial difficulties that are often linked to problematic personality traits/patterns and that result in significant and persistent mental status changes. For example, reassessment might be indicated for a patient with borderline personality disorder who has new-onset or worsening cognitive and/or psychiatric complaints/symptoms after sustaining a head injury while intoxicated and embroiled in a domestic conflict triggered by anger and fears related to abandonment and separation.

Reevaluation also should be considered when a patient with a personality disorder has had a baseline assessment and subsequently completes an intensive, long-term treatment program that is likely to improve their clinical status. In this context, retesting may help document these gains. Examples of such programs/services include residential psychiatric and/or substance abuse care, object relational/psychodynamically-based psychotherapy, an extended course of dialectical behavioral therapy, or a related coping skills/distress tolerance psychotherapy.

Continue to: Contraindications for reassessment

Contraindications for reassessment

Retesting generally is not indicated in the following circumstances:

Patients with advanced major neurocognitive disorder. Reassessment is not indicated for such patients when there are no new questions regarding diagnosis, prognosis, level of care, and/or related disposition issues.

Patients with transient episodes of poor functioning. For the most part, reassessment is not helpful for patients with well-established diagnoses and treatment plans who, based on their history, experience time-limited, recurrent episodes of poor functioning and then reliably return to their baseline with ongoing psychiatric care. This includes patients with borderline personality disorder and other personality difficulties with histories of transient decompensation in response to psychosocial and psychodynamic triggers.

Patients who do not improve or worsen over time. Reassessment is not indicated when there has been no clear, sustained improvement or worsening of a patient’s clinical status over an extended time, and a protracted change is not anticipated. In this situation, reassessment is unlikely to yield clinically useful information beyond what is already known or meaningfully impact case formulation and treatment planning.

The Table^9-14 summarizes the relative indications and contraindications for psychological/neuropsychological reexamination.

Continue to: Time frames for reassessment

 

 

Time frames for reassessment

Time frames for retesting vary considerably depending on factors such as diagnostic status, longitudinal course, treatment parameters, and recent/current life circumstances.

While empirical data is lacking regarding this matter, based on clinical experience, reevaluation in 18 to 24 months is generally appropriate for patients with neuro­psychiatric conditions who are likely to gradually improve or slowly worsen over this time. Still, reexamination can be sooner (within 12 to 18 months) for patients who have experienced a more rapid and steep negative change in clinical status than initially anticipated.

For most patients with major mental illness, reexamination in 3 to 5 years is probably a reasonable time interval, barring a poorly understood and clinically significant negative change in functioning that warrants a shorter time frame. This suggested time frame would allow for sufficient time to better gauge improvement, stability, or deterioration in functioning and whether the reason(s) for referral have evolved. On the other hand, this time interval is somewhat arbitrary given the lack of empirical data. Therefore, on a case-by-case basis, it would be helpful for psychiatrists to consult with their patients and preferably with the psychologist who completed the baseline evaluation to determine a reasonable interval between assessments.

For patients who have undergone long-term/intensive treatment, reassessment in 3 or 6 months to as long as 1 year after the patient completes the program should be considered. Patients who undergo medical interventions such as neurosurgery or ECT—which can be associated with short-term, at least partially reversible negative effects on mental status—reassessment usually is most helpful when initiated as one or more screening level examinations for several weeks, followed by a comprehensive psychometric reassessment at the 3- to 6-month mark.

Suggestions for future research

Additional research is needed to ascertain the attitudes and opinions of psychiatrists and other physicians who use psychometric test data regarding how psychologists can most effectively communicate a recommendation for reassessment in their reports and clarify the ways psychiatrists can productively address this issue with their patients. Survey research of this kind should include questions about the frequency with which psychiatrists formally refer patients for retesting, and estimates of the rate of follow-through.

Continue to: It also would be desirable...

It also would be desirable to investigate factors that may facilitate follow-through with recommendations for reassessment, or, conversely, identify reasons that psychiatrists and their patients may decide to forgo reassessment. It would be important to try to obtain information regarding the optimum time frames for such reevaluation, depending on the patient’s circumstances and other variables. Evidence-based data pertaining to these issues would contribute to the development of consensus guidelines and a standard of care for psychological/neuropsychological test reevaluation.

Bottom Line

Only a very small percentage of patients referred for follow-up psychological/ neuropsychological test reevaluation actually undergo reexamination. Such retesting may be most helpful for certain patient populations, such as those who are likely to soon improve or worsen, were referred based on a family history of major cognitive disorder but have no concerning findings on baseline testing, or are undergoing a substantial life transition.

Related Resources

• Thom R, Farrell HM. Neuroimaging in psychiatry: potentials and pitfalls. Current Psychiatry. 2019;18(12):27-28;33-34.
• Papakostas GI. Cognitive symptoms in patients with major depressive disorder and their implications for clinical practice. J Clin Psychiatry. 2014;75(1):8-14.
• American Board of Professional Neuropsychology. https://abn-board.com

The evolution of illness prevention, diagnosis, and treatment has involved an increased appreciation for the clinical utility of longitudinal assessment. This has included the implementation of screening evaluations for high base rate medical conditions, such as cancer, that involve considerable morbidity and mortality.

Unfortunately, the mental health professions have been slow to embrace this approach. Baseline assessment with psychological/neuropsychological screening tests and more comprehensive test batteries to clarify diagnostic status and facilitate treatment planning is far more the exception than the rule in mental health care. This seems to be the case despite the strong evidence supporting this practice as well as multiple surveys indicating that psychiatrists and other physicians report a high level of satisfaction with the findings and recommendations of psychological/neuropsychological test reports.^1-3

There is a substantial literature that reviews the relative indications and contraindications for initial psychological/neuropsychological test evaluations.^4-7 However, there is a paucity of clinical and evidence-based information regarding criteria for follow-up assessment. Moreover, there are no consensus guidelines to inform decision-making regarding this issue.

In general, good clinical practice for baseline assessment and reexamination should include administration of both psychological and neuropsychological tests. Based on clinical experience, this article addresses the relative indications and contraindications for psychological/neuropsychological test reassessment of adults seen in psychiatric care. It also outlines suggested time frames for such reevaluations, based on the patient’s clinical status and circumstances.

Why are patients not referred for reassessment more often?

There are several reasons patients are not referred for follow-up testing, beginning with the failure, at times, of the psychologist to state in the recommendations section of the test report whether a reassessment is indicated, under what circumstances, and within what time frame. Empirical data is lacking, but predicated on clinical experience, even when a strong and unequivocal recommendation is made for reassessment, only a very small percentage of patients are seen for follow-up evaluation.

There are numerous reasons why this occurs. The patient and/or the psychiatrist may overlook or forget about the recommendation for reassessment, particularly if it was embedded in a lengthy list of recommendations and the suggested time frame for the reassessment was several years away. The patient and the psychiatrist may decide against going forward with a reexamination, for a variety of substantive reasons. The patient might decline, against medical advice, to be retested. The patient may fail to make or keep an appointment for the follow-up reexamination. The patient might leave treatment and become lost to follow-up. The patient might not be able to find an appropriate psychologist. The insurance company may decline to authorize follow-up testing.⁸

Indications for reevaluation

Follow-up testing generally is indicated in the following circumstances:

Patients who are likely to soon improve or worsen. Reassessment is indicated when, based on the initial evaluation, the patient has been identified as having a neuropsychiatric disorder that is likely to improve or worsen over the next year or 2 due to the natural trajectory of the condition and the degree to which it may respond to treatment.

Continue to: Patients who are likely...

Patients who are likely to improve include those with mental status changes referable to ≥1 medical and/or neuropsychiatric factors that are considered at least partially treatable and reversible. Patients who fall within this category include those who have mild to moderately severe head trauma or stroke, have a suspected or known medication- or substance-induced altered mental status, appear to have depression-related cognitive difficulties, or have an initial or recurrent episode of idiopathic psychosis.

Patients whose conditions can be expected to worsen over time include those with a mild neurocognitive disorder or major neuro­cognitive disorder of mild severity that is considered referable to a progressive neurodegenerative illness such as Alzheimer’s disease based on family and personal history, their psychometric test profile, and other factors, including findings from positron emission tomography scanning.

Older patients who were referred primarily due to a strong family history of major neurocognitive disorder but with no clear-cut concerning findings on baseline testing warrant reevaluation in the event of the emergence of significant cognitive and/or psychiatric symptoms and/or a functional decline since the baseline examination.

Patients who have been seen for initial test evaluations prior to interventions such as neuro­surgery (including psychosurgery), electroconvulsive therapy (ECT), transcranial magnetic stimulation, cognitive rehabilitation, etc.

Patients undergoing a substantial transition. Reevaluation is appropriate for a broad range of patients experiencing difficulties when undergoing a significant lifestyle transition or change in level of care. This includes patients considering a return to school or work after a prolonged absence due to neuropsychiatric illness, or for whom there are questions regarding the need for a change in their level of everyday care. The latter includes patients who are returning to home care from assisted living, or transferring from home-based services to assisted living or a skilled nursing facility.

Continue to: What about patients with psychiatric disorders?

What about patients with psychiatric disorders? A “grey area” pertains to reassessment of patients with neuropsychiatric disorders such as schizophrenia and related psychotic disorders, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Patients with these conditions often have high rates of cognitive/neuropsychological impairment on baseline testing, even when they appear to be improving from a psychiatric perspective, are reasonably stable, and may even be in remission.^9-12

These deficits are frequently a mix of pre-illness, prodromal, and early-stage illness– related neurocognitive difficulties that, for the most part, remain stable over time. That said, there is emerging evidence of worsening cognitive change over time following a first episode of psychosis for some patients with schizophrenia.¹³

In general, reevaluation should be considered for patients with a family and/or personal history of cognitive/neuropsychological impairment, structural brain abnormalities on neuroimaging, a concerning cognitive/neuropsychological profile, or any other factors that raise the index of suspicion for a possible progressive deteriorative course of illness.^13,14

Patients with personality disorders who have had a baseline psychometric evaluation do not clearly warrant reassessment unless they develop medical and/or psychosocial difficulties that are often linked to problematic personality traits/patterns and that result in significant and persistent mental status changes. For example, reassessment might be indicated for a patient with borderline personality disorder who has new-onset or worsening cognitive and/or psychiatric complaints/symptoms after sustaining a head injury while intoxicated and embroiled in a domestic conflict triggered by anger and fears related to abandonment and separation.

Reevaluation also should be considered when a patient with a personality disorder has had a baseline assessment and subsequently completes an intensive, long-term treatment program that is likely to improve their clinical status. In this context, retesting may help document these gains. Examples of such programs/services include residential psychiatric and/or substance abuse care, object relational/psychodynamically-based psychotherapy, an extended course of dialectical behavioral therapy, or a related coping skills/distress tolerance psychotherapy.

Continue to: Contraindications for reassessment

Contraindications for reassessment

Retesting generally is not indicated in the following circumstances:

Patients with advanced major neurocognitive disorder. Reassessment is not indicated for such patients when there are no new questions regarding diagnosis, prognosis, level of care, and/or related disposition issues.

Patients with transient episodes of poor functioning. For the most part, reassessment is not helpful for patients with well-established diagnoses and treatment plans who, based on their history, experience time-limited, recurrent episodes of poor functioning and then reliably return to their baseline with ongoing psychiatric care. This includes patients with borderline personality disorder and other personality difficulties with histories of transient decompensation in response to psychosocial and psychodynamic triggers.

Patients who do not improve or worsen over time. Reassessment is not indicated when there has been no clear, sustained improvement or worsening of a patient’s clinical status over an extended time, and a protracted change is not anticipated. In this situation, reassessment is unlikely to yield clinically useful information beyond what is already known or meaningfully impact case formulation and treatment planning.

The Table^9-14 summarizes the relative indications and contraindications for psychological/neuropsychological reexamination.

Continue to: Time frames for reassessment

 

 

Time frames for reassessment

Time frames for retesting vary considerably depending on factors such as diagnostic status, longitudinal course, treatment parameters, and recent/current life circumstances.

While empirical data is lacking regarding this matter, based on clinical experience, reevaluation in 18 to 24 months is generally appropriate for patients with neuro­psychiatric conditions who are likely to gradually improve or slowly worsen over this time. Still, reexamination can be sooner (within 12 to 18 months) for patients who have experienced a more rapid and steep negative change in clinical status than initially anticipated.

For most patients with major mental illness, reexamination in 3 to 5 years is probably a reasonable time interval, barring a poorly understood and clinically significant negative change in functioning that warrants a shorter time frame. This suggested time frame would allow for sufficient time to better gauge improvement, stability, or deterioration in functioning and whether the reason(s) for referral have evolved. On the other hand, this time interval is somewhat arbitrary given the lack of empirical data. Therefore, on a case-by-case basis, it would be helpful for psychiatrists to consult with their patients and preferably with the psychologist who completed the baseline evaluation to determine a reasonable interval between assessments.

For patients who have undergone long-term/intensive treatment, reassessment in 3 or 6 months to as long as 1 year after the patient completes the program should be considered. Patients who undergo medical interventions such as neurosurgery or ECT—which can be associated with short-term, at least partially reversible negative effects on mental status—reassessment usually is most helpful when initiated as one or more screening level examinations for several weeks, followed by a comprehensive psychometric reassessment at the 3- to 6-month mark.

Suggestions for future research

Additional research is needed to ascertain the attitudes and opinions of psychiatrists and other physicians who use psychometric test data regarding how psychologists can most effectively communicate a recommendation for reassessment in their reports and clarify the ways psychiatrists can productively address this issue with their patients. Survey research of this kind should include questions about the frequency with which psychiatrists formally refer patients for retesting, and estimates of the rate of follow-through.

Continue to: It also would be desirable...

It also would be desirable to investigate factors that may facilitate follow-through with recommendations for reassessment, or, conversely, identify reasons that psychiatrists and their patients may decide to forgo reassessment. It would be important to try to obtain information regarding the optimum time frames for such reevaluation, depending on the patient’s circumstances and other variables. Evidence-based data pertaining to these issues would contribute to the development of consensus guidelines and a standard of care for psychological/neuropsychological test reevaluation.

Bottom Line

Only a very small percentage of patients referred for follow-up psychological/ neuropsychological test reevaluation actually undergo reexamination. Such retesting may be most helpful for certain patient populations, such as those who are likely to soon improve or worsen, were referred based on a family history of major cognitive disorder but have no concerning findings on baseline testing, or are undergoing a substantial life transition.

Related Resources

• Thom R, Farrell HM. Neuroimaging in psychiatry: potentials and pitfalls. Current Psychiatry. 2019;18(12):27-28;33-34.
• Papakostas GI. Cognitive symptoms in patients with major depressive disorder and their implications for clinical practice. J Clin Psychiatry. 2014;75(1):8-14.
• American Board of Professional Neuropsychology. https://abn-board.com

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

rfranki@mdedge.com

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

rfranki@mdedge.com

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

rfranki@mdedge.com

The U.S. Food and Drug Administration has expanded the indication for brivaracetam (Briviact, UCB) as both monotherapy or adjunctive therapy for partial-onset seizures in patients as young as 1 month of age.

All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.

The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.

In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.

“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.

“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
 

Safety profile

Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”

The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.

In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.

Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.

Patients should be advised to report these symptoms immediately to a health care professional, the company noted.

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

The U.S. Food and Drug Administration has expanded the indication for brivaracetam (Briviact, UCB) as both monotherapy or adjunctive therapy for partial-onset seizures in patients as young as 1 month of age.

All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.

The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.

In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.

“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.

“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
 

Safety profile

Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”

The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.

In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.

Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.

Patients should be advised to report these symptoms immediately to a health care professional, the company noted.

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

The U.S. Food and Drug Administration has expanded the indication for brivaracetam (Briviact, UCB) as both monotherapy or adjunctive therapy for partial-onset seizures in patients as young as 1 month of age.

All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.

The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.

In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.

“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.

“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
 

Safety profile

Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”

The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.

In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.

Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.

Patients should be advised to report these symptoms immediately to a health care professional, the company noted.

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

Carotid artery stenting (CAS) and carotid endarterectomy (CEA) provided comparable outcomes over time in asymptomatic patients receiving good medical therapy in the largest trial to date of what to do with severe carotid artery narrowing that is yet to cause a stroke.

aaM Photography, Ltd./iStock

Among more than 3,600 patients, stenting and surgery performed by experienced physicians involved a 1.0% risk for causing disabling stroke or death within 30 days.

The annual rate of fatal or disabling strokes was about 0.5% with either procedure over an average 5 years’ follow-up – essentially halving the annual stroke risk had neither procedure been performed, according to Alison Halliday, MD, principal investigator of the Asymptomatic Carotid Surgery Trial-2 (ACST-2).

The results were reported Aug. 29 in a Hot Line session at the virtual annual congress of the European Society of Cardiology and published simultaneously online in The Lancet.

Session chair Gilles Montalescot, MD, Sorbonne University, Paris, noted that ACST-2 doubled the number of randomly assigned patients with asymptomatic carotid stenosis studied in previous trials, “so, a huge contribution to the evidence base in this field and apparently good news for both revascularization techniques.”
 

Thirty-day and 5-year outcomes

The trial was conducted in 33 countries between January 2008 and December 2020, enrolling 3,625 patients (70% were male; mean age, 70 years) with carotid stenosis of at least 60% on ultrasonography, in whom stenting or surgery was suitable but both the doctor and patient were “substantially uncertain” which procedure to prefer.

Among the 1,811 patients assigned to stenting, 87% underwent the procedure at a median of 14 days; 6% crossed over to surgery, typically because of a highly calcified lesion or a more tortuous carotid than anticipated; and 6% had no intervention.

Among the 1,814 patients assigned to surgery, 92% had the procedure at a median of 14 days; 3% crossed over to stenting, typically because of patient or doctor preference or reluctance to undergo general anesthesia; and 4% had no intervention.

Patients without complications who had stenting stayed on average 1 day less than did those undergoing surgery.

During an earlier press briefing, Dr. Halliday highlighted the need for procedural competency and said doctors had to submit a record of their CEA or CAS experience and, consistent with current guidelines, had to demonstrate an independently verified stroke or death rate of 6% or less for symptomatic patients and 3% or lower for asymptomatic patients.

The results showed the 30-day risk for death, myocardial infarction (MI), or any stroke was 3.9% with carotid stenting and 3.2% with surgery (P = .26).

But with stenting, there was a slightly higher risk for procedural nondisabling strokes (48 vs. 29; P = .03), including 15 strokes vs. 5 strokes, respectively, that left patients with no residual symptoms. This is “consistent with large, recent nationally representative registry data,” observed Dr. Halliday, of the University of Oxford (England).

For those undergoing surgery, cranial nerve palsies were reported in 5.4% vs. no patients undergoing stenting.

At 5 years, the nonprocedural fatal or disabling stroke rate was 2.5% in each group (rate ratio [RR], 0.98; P = .91), with any nonprocedural stroke occurring in 5.3% of patients with stenting vs. 4.5% with surgery (RR, 1.16; P = .33).

The investigators performed a meta-analysis combining the ACST-2 results with those of eight prior trials (four in asymptomatic and four in symptomatic patients) that yielded a similar nonsignificant result for any nonprocedural stroke (RR, 1.11; P = .21).

Based on the results from ACST-2 plus the major trials, stenting and surgery involve “similar risks and similar benefits,” Dr. Halliday concluded.

Discussant Marco Roffi, MD, University Hospital of Geneva, said, “In centers with documented expertise, carotid artery stenting should be offered as an alternative to carotid endarterectomy in patients with asymptomatic stenosis and suitable anatomy.”

While the trial provides “good news” for patients, he pointed out that a reduction in the sample size from 5,000 to 3,625 limited the statistical power and that enrollment over a long period of time may have introduced confounders, such as changes in equipment technique, and medical therapy.

Also, many centers enrolled few patients, raising the concern over low-volume centers and operators, Dr. Roffi said. “We know that 8% of the centers enrolled 39% of the patients,” and “information on the credentialing and experience of the interventionalists was limited.”

Further, a lack of systematic MI assessment may have favored the surgery group, and more recent developments in stenting with the potential of reducing periprocedural stroke were rarely used, such as proximal emboli protection in only 15% and double-layer stents in 11%.

Friedhelm Beyersdorf, MD, University Hospital of Freiburg, Germany, said that, as a vascular surgeon, he finds it understandable that there might be a higher incidence of nonfatal strokes when treating carotid stenosis with stents, given the vulnerability of these lesions.

“Nevertheless, the main conclusion from the entire study is that carotid artery treatment is extremely safe, it has to be done in order to avoid strokes, and, obviously, there seems to be an advantage for surgery in terms of nondisabling stroke,” he said.

Session chair Dr. Montalescot, however, said that what the study cannot address – and what was the subject of many online audience comments – is whether either intervention should be performed in these patients. 

Unlike earlier trials comparing interventions to medical therapy, Dr. Halliday said ACST-2 enrolled patients for whom the decision had been made that revascularization was needed. In addition, 99%-100% were receiving antithrombotic therapy at baseline, 85%-90% were receiving antihypertensives, and about 85% were taking statins.

Longer-term follow-up should provide a better picture of the nonprocedural stroke risk, with patients asked annually about exactly what medications and doses they are taking, she said.

“We will have an enormous list of exactly what’s gone on and the intensity of that therapy, which is, of course, much more intense than when we carried out our first trial. But these were people in whom a procedure was thought to be necessary,” she noted.

When asked during the press conference which procedure she would choose, Dr. Halliday, a surgeon, observed that patient preference is important but that the nature of the lesion itself often determines the optimal choice.

“If you know the competence of the people doing it is equal, then the less invasive procedure – providing it has good long-term viability, and that’s why we’re following for 10 years – is the more important,” she added.

The study was funded by the UK Medical Research Council and Health Technology Assessment Programme. Dr. Halliday reports no relevant financial relationships.

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

Carotid artery stenting (CAS) and carotid endarterectomy (CEA) provided comparable outcomes over time in asymptomatic patients receiving good medical therapy in the largest trial to date of what to do with severe carotid artery narrowing that is yet to cause a stroke.

aaM Photography, Ltd./iStock

Among more than 3,600 patients, stenting and surgery performed by experienced physicians involved a 1.0% risk for causing disabling stroke or death within 30 days.

The annual rate of fatal or disabling strokes was about 0.5% with either procedure over an average 5 years’ follow-up – essentially halving the annual stroke risk had neither procedure been performed, according to Alison Halliday, MD, principal investigator of the Asymptomatic Carotid Surgery Trial-2 (ACST-2).

The results were reported Aug. 29 in a Hot Line session at the virtual annual congress of the European Society of Cardiology and published simultaneously online in The Lancet.

Session chair Gilles Montalescot, MD, Sorbonne University, Paris, noted that ACST-2 doubled the number of randomly assigned patients with asymptomatic carotid stenosis studied in previous trials, “so, a huge contribution to the evidence base in this field and apparently good news for both revascularization techniques.”
 

Thirty-day and 5-year outcomes

The trial was conducted in 33 countries between January 2008 and December 2020, enrolling 3,625 patients (70% were male; mean age, 70 years) with carotid stenosis of at least 60% on ultrasonography, in whom stenting or surgery was suitable but both the doctor and patient were “substantially uncertain” which procedure to prefer.

Among the 1,811 patients assigned to stenting, 87% underwent the procedure at a median of 14 days; 6% crossed over to surgery, typically because of a highly calcified lesion or a more tortuous carotid than anticipated; and 6% had no intervention.

Among the 1,814 patients assigned to surgery, 92% had the procedure at a median of 14 days; 3% crossed over to stenting, typically because of patient or doctor preference or reluctance to undergo general anesthesia; and 4% had no intervention.

Patients without complications who had stenting stayed on average 1 day less than did those undergoing surgery.

During an earlier press briefing, Dr. Halliday highlighted the need for procedural competency and said doctors had to submit a record of their CEA or CAS experience and, consistent with current guidelines, had to demonstrate an independently verified stroke or death rate of 6% or less for symptomatic patients and 3% or lower for asymptomatic patients.

The results showed the 30-day risk for death, myocardial infarction (MI), or any stroke was 3.9% with carotid stenting and 3.2% with surgery (P = .26).

But with stenting, there was a slightly higher risk for procedural nondisabling strokes (48 vs. 29; P = .03), including 15 strokes vs. 5 strokes, respectively, that left patients with no residual symptoms. This is “consistent with large, recent nationally representative registry data,” observed Dr. Halliday, of the University of Oxford (England).

For those undergoing surgery, cranial nerve palsies were reported in 5.4% vs. no patients undergoing stenting.

At 5 years, the nonprocedural fatal or disabling stroke rate was 2.5% in each group (rate ratio [RR], 0.98; P = .91), with any nonprocedural stroke occurring in 5.3% of patients with stenting vs. 4.5% with surgery (RR, 1.16; P = .33).

The investigators performed a meta-analysis combining the ACST-2 results with those of eight prior trials (four in asymptomatic and four in symptomatic patients) that yielded a similar nonsignificant result for any nonprocedural stroke (RR, 1.11; P = .21).

Based on the results from ACST-2 plus the major trials, stenting and surgery involve “similar risks and similar benefits,” Dr. Halliday concluded.

Discussant Marco Roffi, MD, University Hospital of Geneva, said, “In centers with documented expertise, carotid artery stenting should be offered as an alternative to carotid endarterectomy in patients with asymptomatic stenosis and suitable anatomy.”

While the trial provides “good news” for patients, he pointed out that a reduction in the sample size from 5,000 to 3,625 limited the statistical power and that enrollment over a long period of time may have introduced confounders, such as changes in equipment technique, and medical therapy.

Also, many centers enrolled few patients, raising the concern over low-volume centers and operators, Dr. Roffi said. “We know that 8% of the centers enrolled 39% of the patients,” and “information on the credentialing and experience of the interventionalists was limited.”

Further, a lack of systematic MI assessment may have favored the surgery group, and more recent developments in stenting with the potential of reducing periprocedural stroke were rarely used, such as proximal emboli protection in only 15% and double-layer stents in 11%.

Friedhelm Beyersdorf, MD, University Hospital of Freiburg, Germany, said that, as a vascular surgeon, he finds it understandable that there might be a higher incidence of nonfatal strokes when treating carotid stenosis with stents, given the vulnerability of these lesions.

“Nevertheless, the main conclusion from the entire study is that carotid artery treatment is extremely safe, it has to be done in order to avoid strokes, and, obviously, there seems to be an advantage for surgery in terms of nondisabling stroke,” he said.

Session chair Dr. Montalescot, however, said that what the study cannot address – and what was the subject of many online audience comments – is whether either intervention should be performed in these patients. 

Unlike earlier trials comparing interventions to medical therapy, Dr. Halliday said ACST-2 enrolled patients for whom the decision had been made that revascularization was needed. In addition, 99%-100% were receiving antithrombotic therapy at baseline, 85%-90% were receiving antihypertensives, and about 85% were taking statins.

Longer-term follow-up should provide a better picture of the nonprocedural stroke risk, with patients asked annually about exactly what medications and doses they are taking, she said.

“We will have an enormous list of exactly what’s gone on and the intensity of that therapy, which is, of course, much more intense than when we carried out our first trial. But these were people in whom a procedure was thought to be necessary,” she noted.

When asked during the press conference which procedure she would choose, Dr. Halliday, a surgeon, observed that patient preference is important but that the nature of the lesion itself often determines the optimal choice.

“If you know the competence of the people doing it is equal, then the less invasive procedure – providing it has good long-term viability, and that’s why we’re following for 10 years – is the more important,” she added.

The study was funded by the UK Medical Research Council and Health Technology Assessment Programme. Dr. Halliday reports no relevant financial relationships.

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

Carotid artery stenting (CAS) and carotid endarterectomy (CEA) provided comparable outcomes over time in asymptomatic patients receiving good medical therapy in the largest trial to date of what to do with severe carotid artery narrowing that is yet to cause a stroke.

aaM Photography, Ltd./iStock

Among more than 3,600 patients, stenting and surgery performed by experienced physicians involved a 1.0% risk for causing disabling stroke or death within 30 days.

The annual rate of fatal or disabling strokes was about 0.5% with either procedure over an average 5 years’ follow-up – essentially halving the annual stroke risk had neither procedure been performed, according to Alison Halliday, MD, principal investigator of the Asymptomatic Carotid Surgery Trial-2 (ACST-2).

The results were reported Aug. 29 in a Hot Line session at the virtual annual congress of the European Society of Cardiology and published simultaneously online in The Lancet.

Session chair Gilles Montalescot, MD, Sorbonne University, Paris, noted that ACST-2 doubled the number of randomly assigned patients with asymptomatic carotid stenosis studied in previous trials, “so, a huge contribution to the evidence base in this field and apparently good news for both revascularization techniques.”
 

Thirty-day and 5-year outcomes

The trial was conducted in 33 countries between January 2008 and December 2020, enrolling 3,625 patients (70% were male; mean age, 70 years) with carotid stenosis of at least 60% on ultrasonography, in whom stenting or surgery was suitable but both the doctor and patient were “substantially uncertain” which procedure to prefer.

Among the 1,811 patients assigned to stenting, 87% underwent the procedure at a median of 14 days; 6% crossed over to surgery, typically because of a highly calcified lesion or a more tortuous carotid than anticipated; and 6% had no intervention.

Among the 1,814 patients assigned to surgery, 92% had the procedure at a median of 14 days; 3% crossed over to stenting, typically because of patient or doctor preference or reluctance to undergo general anesthesia; and 4% had no intervention.

Patients without complications who had stenting stayed on average 1 day less than did those undergoing surgery.

During an earlier press briefing, Dr. Halliday highlighted the need for procedural competency and said doctors had to submit a record of their CEA or CAS experience and, consistent with current guidelines, had to demonstrate an independently verified stroke or death rate of 6% or less for symptomatic patients and 3% or lower for asymptomatic patients.

The results showed the 30-day risk for death, myocardial infarction (MI), or any stroke was 3.9% with carotid stenting and 3.2% with surgery (P = .26).

But with stenting, there was a slightly higher risk for procedural nondisabling strokes (48 vs. 29; P = .03), including 15 strokes vs. 5 strokes, respectively, that left patients with no residual symptoms. This is “consistent with large, recent nationally representative registry data,” observed Dr. Halliday, of the University of Oxford (England).

For those undergoing surgery, cranial nerve palsies were reported in 5.4% vs. no patients undergoing stenting.

At 5 years, the nonprocedural fatal or disabling stroke rate was 2.5% in each group (rate ratio [RR], 0.98; P = .91), with any nonprocedural stroke occurring in 5.3% of patients with stenting vs. 4.5% with surgery (RR, 1.16; P = .33).

The investigators performed a meta-analysis combining the ACST-2 results with those of eight prior trials (four in asymptomatic and four in symptomatic patients) that yielded a similar nonsignificant result for any nonprocedural stroke (RR, 1.11; P = .21).

Based on the results from ACST-2 plus the major trials, stenting and surgery involve “similar risks and similar benefits,” Dr. Halliday concluded.

Discussant Marco Roffi, MD, University Hospital of Geneva, said, “In centers with documented expertise, carotid artery stenting should be offered as an alternative to carotid endarterectomy in patients with asymptomatic stenosis and suitable anatomy.”

While the trial provides “good news” for patients, he pointed out that a reduction in the sample size from 5,000 to 3,625 limited the statistical power and that enrollment over a long period of time may have introduced confounders, such as changes in equipment technique, and medical therapy.

Also, many centers enrolled few patients, raising the concern over low-volume centers and operators, Dr. Roffi said. “We know that 8% of the centers enrolled 39% of the patients,” and “information on the credentialing and experience of the interventionalists was limited.”

Further, a lack of systematic MI assessment may have favored the surgery group, and more recent developments in stenting with the potential of reducing periprocedural stroke were rarely used, such as proximal emboli protection in only 15% and double-layer stents in 11%.

Friedhelm Beyersdorf, MD, University Hospital of Freiburg, Germany, said that, as a vascular surgeon, he finds it understandable that there might be a higher incidence of nonfatal strokes when treating carotid stenosis with stents, given the vulnerability of these lesions.

“Nevertheless, the main conclusion from the entire study is that carotid artery treatment is extremely safe, it has to be done in order to avoid strokes, and, obviously, there seems to be an advantage for surgery in terms of nondisabling stroke,” he said.

Session chair Dr. Montalescot, however, said that what the study cannot address – and what was the subject of many online audience comments – is whether either intervention should be performed in these patients. 

Unlike earlier trials comparing interventions to medical therapy, Dr. Halliday said ACST-2 enrolled patients for whom the decision had been made that revascularization was needed. In addition, 99%-100% were receiving antithrombotic therapy at baseline, 85%-90% were receiving antihypertensives, and about 85% were taking statins.

Longer-term follow-up should provide a better picture of the nonprocedural stroke risk, with patients asked annually about exactly what medications and doses they are taking, she said.

“We will have an enormous list of exactly what’s gone on and the intensity of that therapy, which is, of course, much more intense than when we carried out our first trial. But these were people in whom a procedure was thought to be necessary,” she noted.

When asked during the press conference which procedure she would choose, Dr. Halliday, a surgeon, observed that patient preference is important but that the nature of the lesion itself often determines the optimal choice.

“If you know the competence of the people doing it is equal, then the less invasive procedure – providing it has good long-term viability, and that’s why we’re following for 10 years – is the more important,” she added.

The study was funded by the UK Medical Research Council and Health Technology Assessment Programme. Dr. Halliday reports no relevant financial relationships.

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