MDedge Neurology

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

Printing meds per patient

tomspentys/Unsplash

What if there was a way to get exact doses of a medication, tailored specifically for each and every patient that needed it? Well, apparently it’s as easy as getting them out of a printer.

Researchers from the University of East Anglia in England may have found a new method to do just that.

Currently, medicine is “manufactured in ‘one-size-fits-all’ fashion,” said Dr. Sheng Qi, the research lead. But no patient is exactly the same, so why shouldn’t their medications be just as unique? Research on pharmaceutical 3D printing has been developing over the past 5 years, with the most common method requiring the drug to be put into “spaghetti-like filaments” before printing.

Dr. Qi and his team developed a process that bypasses the filaments, allowing them to 3D-print pills with varied porous structures that can regulate the rate of release of the drug into the body. This could be revolutionary for elderly patients and patients with complicated conditions – who often take many different drugs – to ensure more accurate doses that provide maximum benefits and minimal adverse effects.

Just as a custom-tailored suit perfectly fits the body for which it was made, the ability to tailor medication could have the same effect on a patient’s health. The only difference is what’s coming through the printer would be pills, not fabric.
 

It’s hip to be Pfizered

peterschreiber_media/iStock/Getty Images

COVID-19 vaccination levels are rising, but we’ve heard a rumor that some people are still a bit reticent to participate. So how can physicians get more people to come in for a shot?

Make sure that they’re giving patients the right vaccine, for one thing. And by “right” vaccine, we mean, of course, the cool vaccine. Yes, the Internet has decided that the Pfizer vaccine is cooler than the others, according to the Atlantic.

There is, it seems, such a thing as “Pfizer superiority complex,” the article noted, while adding that, “on TikTok, hundreds of videos use a soundtrack of a woman explaining – slowly, voice full of disdain, like the rudest preschool teacher on Earth – ‘Only hot people get the Pfizer vaccine.’ ” A reporter from Slate was welcomed “to the ruling class” after sharing her upcoming Pfizer vaccination.

For the ultimate test of coolness, we surveyed the LOTME staff about the COVID-19 vaccines they had received. The results? Two Pfizers (coincidentally, the only two who knew what the hell TikTok is), one Moderna, one Johnson & Johnson, and one Godbold’s Vegetable Balsam (coincidentally, the same one who told us to get off his lawn).

And yes, we are checking on that last one.
 

Allergies stink!

Petro Feketa/iStockphoto

A baby’s first bowel movement might mean more than just being the first of many diaper changes.

That particular bowel movement, called meconium, is a mixture of materials that have gone into a baby’s mouth late in the pregnancy, such as skin cells and amniotic fluid. Sounds lovely, right? The contents also include certain biochemicals and gut bacteria, and a lack of these can show an increased risk of allergies, eczema, and asthma.

Studies show that certain gut bacteria actually teach the immune system to accept compounds that are not harmful. Since allergies and other conditions are caused by a person’s immune system telling them harmless compounds are bad, it makes sense that lacking gut bacteria might show potential for developing such conditions.

Charisse Petersen, a researcher at the University of British Columbia in Vancouver, told NewScientist that parents could help decrease the development of allergies by not giving their children antibiotics that aren’t necessary and by letting kids play outside more.

Tom Marrs of King’s College London even noted that having a dog in the house is linked to a lower risk of allergies, so it might be time to get that puppy that the kids have been begging you for all through the pandemic.
 

Indiana Jones and the outhouse of parasites

Photo by Jesse Casana

Some archaeological finds are more impressive than others. Sometimes you find evidence of some long-lost civilization, sometimes you find a 200-year-old outhouse. That was the case with an outhouse buried near Dartmouth College that belonged to Mill Olcott, a wealthy businessman and politician who was a graduate of the college, and his family.

Now, that’s not particularly medically interesting, but the contents of the outhouse were very well preserved. That treasure trove included some fecal samples, and that’s where the story gets good, since they were preserved enough to be analyzed for parasites. Now, researchers know that parasites were very common in urban areas back in those days, when medicinal knowledge and sanitation were still deep in the dark ages, but whether or not people who lived in rural areas, wealthy or not, had them as well was a mystery.

Of course, 200-year-old poop is 200-year-old poop, so, in a task we wouldn’t envy anyone, the samples were rehydrated and run through several sieves to isolate the ancient goodies within. When all was said and done, both tapeworm and whipworm eggs were found, a surprise considering parasitic preference for warmer environments – not something northern New England is known for. But don’t forget, parasites can be your friend, too.

We will probably never know just which member of the Olcott household the poop belonged to, but the researchers noted that it was almost certain the entire house was infected. They added that, without proper infrastructure, even wealth was unable to protect people from disease. Hmm, we can’t think of any relevance that has in today’s world. Nope, absolutely none, since our health infrastructure is literally without flaw.
 

Printing meds per patient

tomspentys/Unsplash

What if there was a way to get exact doses of a medication, tailored specifically for each and every patient that needed it? Well, apparently it’s as easy as getting them out of a printer.

Researchers from the University of East Anglia in England may have found a new method to do just that.

Currently, medicine is “manufactured in ‘one-size-fits-all’ fashion,” said Dr. Sheng Qi, the research lead. But no patient is exactly the same, so why shouldn’t their medications be just as unique? Research on pharmaceutical 3D printing has been developing over the past 5 years, with the most common method requiring the drug to be put into “spaghetti-like filaments” before printing.

Dr. Qi and his team developed a process that bypasses the filaments, allowing them to 3D-print pills with varied porous structures that can regulate the rate of release of the drug into the body. This could be revolutionary for elderly patients and patients with complicated conditions – who often take many different drugs – to ensure more accurate doses that provide maximum benefits and minimal adverse effects.

Just as a custom-tailored suit perfectly fits the body for which it was made, the ability to tailor medication could have the same effect on a patient’s health. The only difference is what’s coming through the printer would be pills, not fabric.
 

It’s hip to be Pfizered

peterschreiber_media/iStock/Getty Images

COVID-19 vaccination levels are rising, but we’ve heard a rumor that some people are still a bit reticent to participate. So how can physicians get more people to come in for a shot?

Make sure that they’re giving patients the right vaccine, for one thing. And by “right” vaccine, we mean, of course, the cool vaccine. Yes, the Internet has decided that the Pfizer vaccine is cooler than the others, according to the Atlantic.

There is, it seems, such a thing as “Pfizer superiority complex,” the article noted, while adding that, “on TikTok, hundreds of videos use a soundtrack of a woman explaining – slowly, voice full of disdain, like the rudest preschool teacher on Earth – ‘Only hot people get the Pfizer vaccine.’ ” A reporter from Slate was welcomed “to the ruling class” after sharing her upcoming Pfizer vaccination.

For the ultimate test of coolness, we surveyed the LOTME staff about the COVID-19 vaccines they had received. The results? Two Pfizers (coincidentally, the only two who knew what the hell TikTok is), one Moderna, one Johnson & Johnson, and one Godbold’s Vegetable Balsam (coincidentally, the same one who told us to get off his lawn).

And yes, we are checking on that last one.
 

Allergies stink!

Petro Feketa/iStockphoto

A baby’s first bowel movement might mean more than just being the first of many diaper changes.

That particular bowel movement, called meconium, is a mixture of materials that have gone into a baby’s mouth late in the pregnancy, such as skin cells and amniotic fluid. Sounds lovely, right? The contents also include certain biochemicals and gut bacteria, and a lack of these can show an increased risk of allergies, eczema, and asthma.

Studies show that certain gut bacteria actually teach the immune system to accept compounds that are not harmful. Since allergies and other conditions are caused by a person’s immune system telling them harmless compounds are bad, it makes sense that lacking gut bacteria might show potential for developing such conditions.

Charisse Petersen, a researcher at the University of British Columbia in Vancouver, told NewScientist that parents could help decrease the development of allergies by not giving their children antibiotics that aren’t necessary and by letting kids play outside more.

Tom Marrs of King’s College London even noted that having a dog in the house is linked to a lower risk of allergies, so it might be time to get that puppy that the kids have been begging you for all through the pandemic.
 

Indiana Jones and the outhouse of parasites

Photo by Jesse Casana

Some archaeological finds are more impressive than others. Sometimes you find evidence of some long-lost civilization, sometimes you find a 200-year-old outhouse. That was the case with an outhouse buried near Dartmouth College that belonged to Mill Olcott, a wealthy businessman and politician who was a graduate of the college, and his family.

Now, that’s not particularly medically interesting, but the contents of the outhouse were very well preserved. That treasure trove included some fecal samples, and that’s where the story gets good, since they were preserved enough to be analyzed for parasites. Now, researchers know that parasites were very common in urban areas back in those days, when medicinal knowledge and sanitation were still deep in the dark ages, but whether or not people who lived in rural areas, wealthy or not, had them as well was a mystery.

Of course, 200-year-old poop is 200-year-old poop, so, in a task we wouldn’t envy anyone, the samples were rehydrated and run through several sieves to isolate the ancient goodies within. When all was said and done, both tapeworm and whipworm eggs were found, a surprise considering parasitic preference for warmer environments – not something northern New England is known for. But don’t forget, parasites can be your friend, too.

We will probably never know just which member of the Olcott household the poop belonged to, but the researchers noted that it was almost certain the entire house was infected. They added that, without proper infrastructure, even wealth was unable to protect people from disease. Hmm, we can’t think of any relevance that has in today’s world. Nope, absolutely none, since our health infrastructure is literally without flaw.
 

Printing meds per patient

tomspentys/Unsplash

What if there was a way to get exact doses of a medication, tailored specifically for each and every patient that needed it? Well, apparently it’s as easy as getting them out of a printer.

Researchers from the University of East Anglia in England may have found a new method to do just that.

Currently, medicine is “manufactured in ‘one-size-fits-all’ fashion,” said Dr. Sheng Qi, the research lead. But no patient is exactly the same, so why shouldn’t their medications be just as unique? Research on pharmaceutical 3D printing has been developing over the past 5 years, with the most common method requiring the drug to be put into “spaghetti-like filaments” before printing.

Dr. Qi and his team developed a process that bypasses the filaments, allowing them to 3D-print pills with varied porous structures that can regulate the rate of release of the drug into the body. This could be revolutionary for elderly patients and patients with complicated conditions – who often take many different drugs – to ensure more accurate doses that provide maximum benefits and minimal adverse effects.

Just as a custom-tailored suit perfectly fits the body for which it was made, the ability to tailor medication could have the same effect on a patient’s health. The only difference is what’s coming through the printer would be pills, not fabric.
 

It’s hip to be Pfizered

peterschreiber_media/iStock/Getty Images

COVID-19 vaccination levels are rising, but we’ve heard a rumor that some people are still a bit reticent to participate. So how can physicians get more people to come in for a shot?

Make sure that they’re giving patients the right vaccine, for one thing. And by “right” vaccine, we mean, of course, the cool vaccine. Yes, the Internet has decided that the Pfizer vaccine is cooler than the others, according to the Atlantic.

There is, it seems, such a thing as “Pfizer superiority complex,” the article noted, while adding that, “on TikTok, hundreds of videos use a soundtrack of a woman explaining – slowly, voice full of disdain, like the rudest preschool teacher on Earth – ‘Only hot people get the Pfizer vaccine.’ ” A reporter from Slate was welcomed “to the ruling class” after sharing her upcoming Pfizer vaccination.

For the ultimate test of coolness, we surveyed the LOTME staff about the COVID-19 vaccines they had received. The results? Two Pfizers (coincidentally, the only two who knew what the hell TikTok is), one Moderna, one Johnson & Johnson, and one Godbold’s Vegetable Balsam (coincidentally, the same one who told us to get off his lawn).

And yes, we are checking on that last one.
 

Allergies stink!

Petro Feketa/iStockphoto

A baby’s first bowel movement might mean more than just being the first of many diaper changes.

That particular bowel movement, called meconium, is a mixture of materials that have gone into a baby’s mouth late in the pregnancy, such as skin cells and amniotic fluid. Sounds lovely, right? The contents also include certain biochemicals and gut bacteria, and a lack of these can show an increased risk of allergies, eczema, and asthma.

Studies show that certain gut bacteria actually teach the immune system to accept compounds that are not harmful. Since allergies and other conditions are caused by a person’s immune system telling them harmless compounds are bad, it makes sense that lacking gut bacteria might show potential for developing such conditions.

Charisse Petersen, a researcher at the University of British Columbia in Vancouver, told NewScientist that parents could help decrease the development of allergies by not giving their children antibiotics that aren’t necessary and by letting kids play outside more.

Tom Marrs of King’s College London even noted that having a dog in the house is linked to a lower risk of allergies, so it might be time to get that puppy that the kids have been begging you for all through the pandemic.
 

Indiana Jones and the outhouse of parasites

Photo by Jesse Casana

Some archaeological finds are more impressive than others. Sometimes you find evidence of some long-lost civilization, sometimes you find a 200-year-old outhouse. That was the case with an outhouse buried near Dartmouth College that belonged to Mill Olcott, a wealthy businessman and politician who was a graduate of the college, and his family.

Now, that’s not particularly medically interesting, but the contents of the outhouse were very well preserved. That treasure trove included some fecal samples, and that’s where the story gets good, since they were preserved enough to be analyzed for parasites. Now, researchers know that parasites were very common in urban areas back in those days, when medicinal knowledge and sanitation were still deep in the dark ages, but whether or not people who lived in rural areas, wealthy or not, had them as well was a mystery.

Of course, 200-year-old poop is 200-year-old poop, so, in a task we wouldn’t envy anyone, the samples were rehydrated and run through several sieves to isolate the ancient goodies within. When all was said and done, both tapeworm and whipworm eggs were found, a surprise considering parasitic preference for warmer environments – not something northern New England is known for. But don’t forget, parasites can be your friend, too.

We will probably never know just which member of the Olcott household the poop belonged to, but the researchers noted that it was almost certain the entire house was infected. They added that, without proper infrastructure, even wealth was unable to protect people from disease. Hmm, we can’t think of any relevance that has in today’s world. Nope, absolutely none, since our health infrastructure is literally without flaw.
 

I’ve taken care of both Bill and his wife for a few years. They’re a sweet couple, each with their own neurological issues. Bill has also battled depression on and off over time. He can be a challenge, and I’ve never envied his psychiatrist.

Bill committed suicide in the final week of April.

Patient deaths are unavoidable in medicine. It’s part of the job. Suicides, though less common, also happen. Sometimes they’re related to a sad diagnosis we’ve made, but more commonly (as in Bill’s case) they result from demons we had no control over.

I had a patient commit suicide about 6 months after I started my practice, and probably average one every 2 years (that I hear about) since then. They’re still the deaths that surprise me the most, make me take pause for a few minutes, even after doing this for 23 years.

Suicide is as old as humanity, and gets worse during difficult societal and economic times. It disproportionately affects doctors, dentists, veterinarians, and police officers, and leaves devastated families and friends in its wake.

Death because of the progression of time and disease is never easy, but perhaps more psychologically acceptable to those left behind. Death because of a tragic accident at any age is more difficult.

But when the person involved makes a conscious decision to end his or her own life, the effects on those left behind are terrible. Wondering why, questioning if they could have done something different, and, as with any loss, grieving.

Suicide remains extremely difficult to prevent. In a world where major advances have been made in many areas of medicine, including mental health, death from despair shows no sign of abating.

Maybe it’s part of the price of sentience and reason. Or civilization. I doubt it will ever stop being a public health issue, no matter how many other diseases we cure.

But, as I write a letter to Bill’s wife, that’s little consolation for those they’ve left behind.

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

I’ve taken care of both Bill and his wife for a few years. They’re a sweet couple, each with their own neurological issues. Bill has also battled depression on and off over time. He can be a challenge, and I’ve never envied his psychiatrist.

Bill committed suicide in the final week of April.

Patient deaths are unavoidable in medicine. It’s part of the job. Suicides, though less common, also happen. Sometimes they’re related to a sad diagnosis we’ve made, but more commonly (as in Bill’s case) they result from demons we had no control over.

I had a patient commit suicide about 6 months after I started my practice, and probably average one every 2 years (that I hear about) since then. They’re still the deaths that surprise me the most, make me take pause for a few minutes, even after doing this for 23 years.

Suicide is as old as humanity, and gets worse during difficult societal and economic times. It disproportionately affects doctors, dentists, veterinarians, and police officers, and leaves devastated families and friends in its wake.

Death because of the progression of time and disease is never easy, but perhaps more psychologically acceptable to those left behind. Death because of a tragic accident at any age is more difficult.

But when the person involved makes a conscious decision to end his or her own life, the effects on those left behind are terrible. Wondering why, questioning if they could have done something different, and, as with any loss, grieving.

Suicide remains extremely difficult to prevent. In a world where major advances have been made in many areas of medicine, including mental health, death from despair shows no sign of abating.

Maybe it’s part of the price of sentience and reason. Or civilization. I doubt it will ever stop being a public health issue, no matter how many other diseases we cure.

But, as I write a letter to Bill’s wife, that’s little consolation for those they’ve left behind.

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

I’ve taken care of both Bill and his wife for a few years. They’re a sweet couple, each with their own neurological issues. Bill has also battled depression on and off over time. He can be a challenge, and I’ve never envied his psychiatrist.

Bill committed suicide in the final week of April.

Patient deaths are unavoidable in medicine. It’s part of the job. Suicides, though less common, also happen. Sometimes they’re related to a sad diagnosis we’ve made, but more commonly (as in Bill’s case) they result from demons we had no control over.

I had a patient commit suicide about 6 months after I started my practice, and probably average one every 2 years (that I hear about) since then. They’re still the deaths that surprise me the most, make me take pause for a few minutes, even after doing this for 23 years.

Suicide is as old as humanity, and gets worse during difficult societal and economic times. It disproportionately affects doctors, dentists, veterinarians, and police officers, and leaves devastated families and friends in its wake.

Death because of the progression of time and disease is never easy, but perhaps more psychologically acceptable to those left behind. Death because of a tragic accident at any age is more difficult.

But when the person involved makes a conscious decision to end his or her own life, the effects on those left behind are terrible. Wondering why, questioning if they could have done something different, and, as with any loss, grieving.

Suicide remains extremely difficult to prevent. In a world where major advances have been made in many areas of medicine, including mental health, death from despair shows no sign of abating.

Maybe it’s part of the price of sentience and reason. Or civilization. I doubt it will ever stop being a public health issue, no matter how many other diseases we cure.

But, as I write a letter to Bill’s wife, that’s little consolation for those they’ve left behind.

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

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

Plasma levels of von Willebrand factor may be a useful biomarker of traumatic brain injury (TBI) and its severity, new research suggests. “Reliable detection of this biomarker at very early time points may allow for prompt TBI detection and therefore intervention,” said study investigator Rachel Elizabeth Thomas, MD, PhD, a neurology resident at the University of Pennsylvania, Philadelphia, while presenting study findings at the American Academy of Neurology’s 2021 annual meeting.

“The level reflects the degree of severity and provides some degree of prognostic information,” she added.
 

A specific marker of acute injury?

Von Willebrand factor is a glycoprotein released in the endothelium in response to local trauma. It plays a part in hemostasis and inflammation and is an indicator of traumatic microvascular injury. Research has shown that it is a biomarker of cerebrovascular pathology. In addition, increased expression of the factor is associated with vascular and neurodegenerative dementia.

The researchers examined whether von Willebrand factor is a biomarker of mild, repetitive TBI. They measured plasma levels of von Willebrand factor in 17 professional boxers before and after boxing bouts.

Eligible participants were between the ages of 18 and 35 years. They had a score of greater than or equal to 1 on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ-3), had competed in at least three 3-minute bouts, and had withstood 25 or more blows to the head.

The investigators compared the plasma levels of von Willebrand factor of the boxers with those of 42 patients who presented to the University of Pennsylvania Trauma Center with TBI and with those of 23 uninjured control persons.

There was no significant difference in plasma levels of von Willebrand factor between boxers before the bout (13.15 µg/mL) and the control persons (6.16 µg/mL). Among the boxers, levels of von Willebrand factor increased by a factor of 1.8 within 30 minutes after bouts, compared with the levels among the control persons. The mean post-bout von Willebrand factor level was 25.09 µg/mL.

“Von Willebrand factor may be more specific for acute injuries, given that it does not seem to stay chronically elevated,” said Dr. Thomas.

In addition, the researchers found a significant positive correlation (r = 0.51; P = .03) between the fold change in plasma von Willebrand factor levels and the number of blows to the head that the athletes sustained.

They also found a significant positive correlation between fold change in von Willebrand factor and RPQ-3 score (r = 0.69; P = .002). These objective and subjective data suggest that levels of von Willebrand factor reflect injury severity, said Dr. Thomas.

Among patients hospitalized with TBI, levels of von Willebrand factor were significantly higher than among control persons (73.2 µg/mL vs. 40.8 µg/mL; P < .0009). The investigators found a linear correlation between plasma von Willebrand factor level and RPQ-3 score (r = 0.24) that was not statistically significant.

Levels of von Willebrand factor among patients hospitalized with TBI were higher on average and demonstrated a greater degree of variability than the levels among boxers immediately after a bout.

“This is not unexpected, given that this group represents a more heterogeneous population with varied forms of acute blunt injury, as compared to the boxers, who have undergone relatively repetitive, milder trauma,” Dr. Thomas said.

The traditional biomarkers of neurotrauma reflect neuronal and glial injury, whereas von Willebrand factor is an indicator of vascular trauma.

“Although on its own, von Willebrand factor is not specific to intracranial vascular injury, paired together with markers such as neurofilament light, GFAP [glial fibrillary acidic protein], and tau, it could be utilized to identify TBI-associated microvascular injury and thus delineate between specific TBI endophenotypes,” said Dr. Thomas. It could distinguish, for example, predominantly neuronal injury from predominantly vascular injury.

Because von Willebrand factor plays a role in the neurovascular unit and is a marker of microvascular injury, the investigators intend to pair measurements of plasma von Willebrand factor with advanced imaging techniques to evaluate cerebral blood flow or cerebrovascular reactivity. Such a study could help determine whether von Willebrand factor levels correlate with the degree of vascular injury and cerebrovascular dysregulation.
 

Point-of-care test?

Commenting on the findings, Kristine O’Phelan, MD, professor of clinical neurology and director of neurocritical care in the department of neurology at the University of Miami, said von Willebrand factor’s likely utility would be as a marker of injury in patients with mild TBI or sports-related concussion.

Imaging and clinical exams do not always reveal these injuries, Dr. O’Phelan added. “Having a biomarker that you can easily test in the blood would be extremely helpful,” she said.

The most exciting part of this study is that it indicates the potential to develop a point-of-care test for use on the athletic field or the battlefield for early detection of mild TBI, she added.

The fact that the test for von Willebrand factor has already been developed is an advantage, said Dr. O’Phelan. The normal and abnormal values of the test are clearly understood. “I do think that they will still need to calibrate it for head injury, because that’s not usually what the test is used for,” said Dr. O’Phelan.

One of the study’s strengths is that the investigators compared patients with TBI with control persons who had exercised, she added, because such a comparison helps clarify the biomarker’s relationship to the injury. Another strength is the application of the test to injuries of various types and of different degrees of severity.

But the biomarker will need to be tested in a larger population, said Dr. O’Phelan. In addition, there is a need to identify the right patient population for this test, as well as the best time frame for its application and potential factors that could confound the test results.

“I do worry a little bit about using early biomarkers for prognosis, particularly in severe TBI, because there’s so many variables that go into outcome,” said Dr. O’Phelan. This test likely would be administered in the first hours after injury, but many factors might affect patients’ outcomes, she added.

One influential factor is age. “If you have a von Willebrand factor of whatever number, that might have different importance in a 30-year-old than in an 80-year-old,” said Dr. O’Phelan. “We need to understand how to interpret those findings better.”

The study was supported by the National Institute for Neurological Disorders and Stroke, the U.S. Department of Defense, and the Pennsylvania Department of Health. Dr. Thomas and Dr. O’Phelan have disclosed no relevant financial relationships.

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

Plasma levels of von Willebrand factor may be a useful biomarker of traumatic brain injury (TBI) and its severity, new research suggests. “Reliable detection of this biomarker at very early time points may allow for prompt TBI detection and therefore intervention,” said study investigator Rachel Elizabeth Thomas, MD, PhD, a neurology resident at the University of Pennsylvania, Philadelphia, while presenting study findings at the American Academy of Neurology’s 2021 annual meeting.

“The level reflects the degree of severity and provides some degree of prognostic information,” she added.
 

A specific marker of acute injury?

Von Willebrand factor is a glycoprotein released in the endothelium in response to local trauma. It plays a part in hemostasis and inflammation and is an indicator of traumatic microvascular injury. Research has shown that it is a biomarker of cerebrovascular pathology. In addition, increased expression of the factor is associated with vascular and neurodegenerative dementia.

The researchers examined whether von Willebrand factor is a biomarker of mild, repetitive TBI. They measured plasma levels of von Willebrand factor in 17 professional boxers before and after boxing bouts.

Eligible participants were between the ages of 18 and 35 years. They had a score of greater than or equal to 1 on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ-3), had competed in at least three 3-minute bouts, and had withstood 25 or more blows to the head.

The investigators compared the plasma levels of von Willebrand factor of the boxers with those of 42 patients who presented to the University of Pennsylvania Trauma Center with TBI and with those of 23 uninjured control persons.

There was no significant difference in plasma levels of von Willebrand factor between boxers before the bout (13.15 µg/mL) and the control persons (6.16 µg/mL). Among the boxers, levels of von Willebrand factor increased by a factor of 1.8 within 30 minutes after bouts, compared with the levels among the control persons. The mean post-bout von Willebrand factor level was 25.09 µg/mL.

“Von Willebrand factor may be more specific for acute injuries, given that it does not seem to stay chronically elevated,” said Dr. Thomas.

In addition, the researchers found a significant positive correlation (r = 0.51; P = .03) between the fold change in plasma von Willebrand factor levels and the number of blows to the head that the athletes sustained.

They also found a significant positive correlation between fold change in von Willebrand factor and RPQ-3 score (r = 0.69; P = .002). These objective and subjective data suggest that levels of von Willebrand factor reflect injury severity, said Dr. Thomas.

Among patients hospitalized with TBI, levels of von Willebrand factor were significantly higher than among control persons (73.2 µg/mL vs. 40.8 µg/mL; P < .0009). The investigators found a linear correlation between plasma von Willebrand factor level and RPQ-3 score (r = 0.24) that was not statistically significant.

Levels of von Willebrand factor among patients hospitalized with TBI were higher on average and demonstrated a greater degree of variability than the levels among boxers immediately after a bout.

“This is not unexpected, given that this group represents a more heterogeneous population with varied forms of acute blunt injury, as compared to the boxers, who have undergone relatively repetitive, milder trauma,” Dr. Thomas said.

The traditional biomarkers of neurotrauma reflect neuronal and glial injury, whereas von Willebrand factor is an indicator of vascular trauma.

“Although on its own, von Willebrand factor is not specific to intracranial vascular injury, paired together with markers such as neurofilament light, GFAP [glial fibrillary acidic protein], and tau, it could be utilized to identify TBI-associated microvascular injury and thus delineate between specific TBI endophenotypes,” said Dr. Thomas. It could distinguish, for example, predominantly neuronal injury from predominantly vascular injury.

Because von Willebrand factor plays a role in the neurovascular unit and is a marker of microvascular injury, the investigators intend to pair measurements of plasma von Willebrand factor with advanced imaging techniques to evaluate cerebral blood flow or cerebrovascular reactivity. Such a study could help determine whether von Willebrand factor levels correlate with the degree of vascular injury and cerebrovascular dysregulation.
 

Point-of-care test?

Commenting on the findings, Kristine O’Phelan, MD, professor of clinical neurology and director of neurocritical care in the department of neurology at the University of Miami, said von Willebrand factor’s likely utility would be as a marker of injury in patients with mild TBI or sports-related concussion.

Imaging and clinical exams do not always reveal these injuries, Dr. O’Phelan added. “Having a biomarker that you can easily test in the blood would be extremely helpful,” she said.

The most exciting part of this study is that it indicates the potential to develop a point-of-care test for use on the athletic field or the battlefield for early detection of mild TBI, she added.

The fact that the test for von Willebrand factor has already been developed is an advantage, said Dr. O’Phelan. The normal and abnormal values of the test are clearly understood. “I do think that they will still need to calibrate it for head injury, because that’s not usually what the test is used for,” said Dr. O’Phelan.

One of the study’s strengths is that the investigators compared patients with TBI with control persons who had exercised, she added, because such a comparison helps clarify the biomarker’s relationship to the injury. Another strength is the application of the test to injuries of various types and of different degrees of severity.

But the biomarker will need to be tested in a larger population, said Dr. O’Phelan. In addition, there is a need to identify the right patient population for this test, as well as the best time frame for its application and potential factors that could confound the test results.

“I do worry a little bit about using early biomarkers for prognosis, particularly in severe TBI, because there’s so many variables that go into outcome,” said Dr. O’Phelan. This test likely would be administered in the first hours after injury, but many factors might affect patients’ outcomes, she added.

One influential factor is age. “If you have a von Willebrand factor of whatever number, that might have different importance in a 30-year-old than in an 80-year-old,” said Dr. O’Phelan. “We need to understand how to interpret those findings better.”

The study was supported by the National Institute for Neurological Disorders and Stroke, the U.S. Department of Defense, and the Pennsylvania Department of Health. Dr. Thomas and Dr. O’Phelan have disclosed no relevant financial relationships.

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

Plasma levels of von Willebrand factor may be a useful biomarker of traumatic brain injury (TBI) and its severity, new research suggests. “Reliable detection of this biomarker at very early time points may allow for prompt TBI detection and therefore intervention,” said study investigator Rachel Elizabeth Thomas, MD, PhD, a neurology resident at the University of Pennsylvania, Philadelphia, while presenting study findings at the American Academy of Neurology’s 2021 annual meeting.

“The level reflects the degree of severity and provides some degree of prognostic information,” she added.
 

A specific marker of acute injury?

Von Willebrand factor is a glycoprotein released in the endothelium in response to local trauma. It plays a part in hemostasis and inflammation and is an indicator of traumatic microvascular injury. Research has shown that it is a biomarker of cerebrovascular pathology. In addition, increased expression of the factor is associated with vascular and neurodegenerative dementia.

The researchers examined whether von Willebrand factor is a biomarker of mild, repetitive TBI. They measured plasma levels of von Willebrand factor in 17 professional boxers before and after boxing bouts.

Eligible participants were between the ages of 18 and 35 years. They had a score of greater than or equal to 1 on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ-3), had competed in at least three 3-minute bouts, and had withstood 25 or more blows to the head.

The investigators compared the plasma levels of von Willebrand factor of the boxers with those of 42 patients who presented to the University of Pennsylvania Trauma Center with TBI and with those of 23 uninjured control persons.

There was no significant difference in plasma levels of von Willebrand factor between boxers before the bout (13.15 µg/mL) and the control persons (6.16 µg/mL). Among the boxers, levels of von Willebrand factor increased by a factor of 1.8 within 30 minutes after bouts, compared with the levels among the control persons. The mean post-bout von Willebrand factor level was 25.09 µg/mL.

“Von Willebrand factor may be more specific for acute injuries, given that it does not seem to stay chronically elevated,” said Dr. Thomas.

In addition, the researchers found a significant positive correlation (r = 0.51; P = .03) between the fold change in plasma von Willebrand factor levels and the number of blows to the head that the athletes sustained.

They also found a significant positive correlation between fold change in von Willebrand factor and RPQ-3 score (r = 0.69; P = .002). These objective and subjective data suggest that levels of von Willebrand factor reflect injury severity, said Dr. Thomas.

Among patients hospitalized with TBI, levels of von Willebrand factor were significantly higher than among control persons (73.2 µg/mL vs. 40.8 µg/mL; P < .0009). The investigators found a linear correlation between plasma von Willebrand factor level and RPQ-3 score (r = 0.24) that was not statistically significant.

Levels of von Willebrand factor among patients hospitalized with TBI were higher on average and demonstrated a greater degree of variability than the levels among boxers immediately after a bout.

“This is not unexpected, given that this group represents a more heterogeneous population with varied forms of acute blunt injury, as compared to the boxers, who have undergone relatively repetitive, milder trauma,” Dr. Thomas said.

The traditional biomarkers of neurotrauma reflect neuronal and glial injury, whereas von Willebrand factor is an indicator of vascular trauma.

“Although on its own, von Willebrand factor is not specific to intracranial vascular injury, paired together with markers such as neurofilament light, GFAP [glial fibrillary acidic protein], and tau, it could be utilized to identify TBI-associated microvascular injury and thus delineate between specific TBI endophenotypes,” said Dr. Thomas. It could distinguish, for example, predominantly neuronal injury from predominantly vascular injury.

Because von Willebrand factor plays a role in the neurovascular unit and is a marker of microvascular injury, the investigators intend to pair measurements of plasma von Willebrand factor with advanced imaging techniques to evaluate cerebral blood flow or cerebrovascular reactivity. Such a study could help determine whether von Willebrand factor levels correlate with the degree of vascular injury and cerebrovascular dysregulation.
 

Point-of-care test?

Commenting on the findings, Kristine O’Phelan, MD, professor of clinical neurology and director of neurocritical care in the department of neurology at the University of Miami, said von Willebrand factor’s likely utility would be as a marker of injury in patients with mild TBI or sports-related concussion.

Imaging and clinical exams do not always reveal these injuries, Dr. O’Phelan added. “Having a biomarker that you can easily test in the blood would be extremely helpful,” she said.

The most exciting part of this study is that it indicates the potential to develop a point-of-care test for use on the athletic field or the battlefield for early detection of mild TBI, she added.

The fact that the test for von Willebrand factor has already been developed is an advantage, said Dr. O’Phelan. The normal and abnormal values of the test are clearly understood. “I do think that they will still need to calibrate it for head injury, because that’s not usually what the test is used for,” said Dr. O’Phelan.

One of the study’s strengths is that the investigators compared patients with TBI with control persons who had exercised, she added, because such a comparison helps clarify the biomarker’s relationship to the injury. Another strength is the application of the test to injuries of various types and of different degrees of severity.

But the biomarker will need to be tested in a larger population, said Dr. O’Phelan. In addition, there is a need to identify the right patient population for this test, as well as the best time frame for its application and potential factors that could confound the test results.

“I do worry a little bit about using early biomarkers for prognosis, particularly in severe TBI, because there’s so many variables that go into outcome,” said Dr. O’Phelan. This test likely would be administered in the first hours after injury, but many factors might affect patients’ outcomes, she added.

One influential factor is age. “If you have a von Willebrand factor of whatever number, that might have different importance in a 30-year-old than in an 80-year-old,” said Dr. O’Phelan. “We need to understand how to interpret those findings better.”

The study was supported by the National Institute for Neurological Disorders and Stroke, the U.S. Department of Defense, and the Pennsylvania Department of Health. Dr. Thomas and Dr. O’Phelan have disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved a higher-dose naloxone hydrochloride nasal spray (Kloxxado) for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

Olivier Le Moal/Getty Images

Kloxxado delivers 8 mg of naloxone into the nasal cavity, which is twice as much as the 4 mg of naloxone contained in Narcan nasal spray.

When administered quickly, naloxone can counter opioid overdose effects, usually within minutes. A higher dose of naloxone provides an additional option for the treatment of opioid overdoses, the FDA said in a news release.

“This approval meets another critical need in combating opioid overdose,” Patrizia Cavazzoni, MD, director, FDA Center for Drug Evaluation and Research, said in the release.

“Addressing the opioid crisis is a top priority for the FDA, and we will continue our efforts to increase access to naloxone and place this important medicine in the hands of those who need it most,” said Dr. Cavazzoni.

In a company news release announcing the approval, manufacturer Hikma Pharmaceuticals noted that a recent survey of community organizations in which the 4-mg naloxone nasal spray had been distributed showed that for 34% of attempted reversals, two or more doses of naloxone were used.

A separate study found that the percentage of overdose-related emergency medical service calls in the United States that led to the administration of multiple doses of naloxone increased to 21% during the period of 2013-2016, which represents a 43% increase over 4 years.

“The approval of Kloxxado is an important step in providing patients, friends, and family members – as well as the public health community – with an important new option for treating opioid overdose,” Brian Hoffmann, president of Hikma Generics, said in the release.

The company expects Kloxxado to available in the second half of 2021.

The FDA approved Kloxxado through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

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

The Food and Drug Administration has approved a higher-dose naloxone hydrochloride nasal spray (Kloxxado) for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

Olivier Le Moal/Getty Images

Kloxxado delivers 8 mg of naloxone into the nasal cavity, which is twice as much as the 4 mg of naloxone contained in Narcan nasal spray.

When administered quickly, naloxone can counter opioid overdose effects, usually within minutes. A higher dose of naloxone provides an additional option for the treatment of opioid overdoses, the FDA said in a news release.

“This approval meets another critical need in combating opioid overdose,” Patrizia Cavazzoni, MD, director, FDA Center for Drug Evaluation and Research, said in the release.

“Addressing the opioid crisis is a top priority for the FDA, and we will continue our efforts to increase access to naloxone and place this important medicine in the hands of those who need it most,” said Dr. Cavazzoni.

In a company news release announcing the approval, manufacturer Hikma Pharmaceuticals noted that a recent survey of community organizations in which the 4-mg naloxone nasal spray had been distributed showed that for 34% of attempted reversals, two or more doses of naloxone were used.

A separate study found that the percentage of overdose-related emergency medical service calls in the United States that led to the administration of multiple doses of naloxone increased to 21% during the period of 2013-2016, which represents a 43% increase over 4 years.

“The approval of Kloxxado is an important step in providing patients, friends, and family members – as well as the public health community – with an important new option for treating opioid overdose,” Brian Hoffmann, president of Hikma Generics, said in the release.

The company expects Kloxxado to available in the second half of 2021.

The FDA approved Kloxxado through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

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

The Food and Drug Administration has approved a higher-dose naloxone hydrochloride nasal spray (Kloxxado) for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

Olivier Le Moal/Getty Images

Kloxxado delivers 8 mg of naloxone into the nasal cavity, which is twice as much as the 4 mg of naloxone contained in Narcan nasal spray.

When administered quickly, naloxone can counter opioid overdose effects, usually within minutes. A higher dose of naloxone provides an additional option for the treatment of opioid overdoses, the FDA said in a news release.

“This approval meets another critical need in combating opioid overdose,” Patrizia Cavazzoni, MD, director, FDA Center for Drug Evaluation and Research, said in the release.

“Addressing the opioid crisis is a top priority for the FDA, and we will continue our efforts to increase access to naloxone and place this important medicine in the hands of those who need it most,” said Dr. Cavazzoni.

In a company news release announcing the approval, manufacturer Hikma Pharmaceuticals noted that a recent survey of community organizations in which the 4-mg naloxone nasal spray had been distributed showed that for 34% of attempted reversals, two or more doses of naloxone were used.

A separate study found that the percentage of overdose-related emergency medical service calls in the United States that led to the administration of multiple doses of naloxone increased to 21% during the period of 2013-2016, which represents a 43% increase over 4 years.

“The approval of Kloxxado is an important step in providing patients, friends, and family members – as well as the public health community – with an important new option for treating opioid overdose,” Brian Hoffmann, president of Hikma Generics, said in the release.

The company expects Kloxxado to available in the second half of 2021.

The FDA approved Kloxxado through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

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

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

LPETTET/Getty Images

At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

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

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

LPETTET/Getty Images

At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

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

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

LPETTET/Getty Images

At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

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

In April 2020, hospitalist Samantha Houston, MD, lost her job at Baptist Memorial Hospital–North, in Oxford, Miss., after she publicly campaigned to get donations of N95 masks for nurses. Dr. Houston filed a lawsuit against the hospital, saying she was improperly fired for speaking out. The lawsuit has not yet gone to trial.

John Fedele/Getty Images

In January 2017, emergency physician Raymond Brovont, MD, was fired by EmCare, an emergency physician staffing company, after reporting understaffing at hospitals with which it contracted in the Kansas City, Mo., area. Dr. Brovont sued EmCare, and the company lost the case. In February 2019, it was ordered to pay him $13.1 million in damages.

These are just two of several cases in recent years in which physicians have spoken out about problems involving patient care and have been sanctioned. Other physicians who see problems choose to stay silent.

Doctors often hesitate to speak out because of the prospect of losing their jobs. A 2013 study of emergency physicians found that nearly 20% reported a possible or real threat to their employment if they expressed concerns about quality of care.

When physicians do not speak openly about important medical issues, the quality of care in their institutions suffers, said a coauthor of the study, Larry D. Weiss, MD, JD, a retired professor of emergency medicine at the University of Maryland, Baltimore.

“Physicians can’t effectively represent patients if they are always thinking they can get fired for what they say,” Dr. Weiss said. “If you don’t have protections like due process, which is often the case, you are less likely to speak out.”

The COVID-19 pandemic put to the test physicians’ ability to speak publicly about troublesome issues. In the first few weeks, health care facilities were struggling to obtain personal protective equipment (PPE) and to create policies that would keep patients and caregivers safe.

Physicians such as Dr. Houston took the initiative to make sure their institutions were taking the right steps against COVID-19 and found themselves at loggerheads with administrators who were concerned that their organizations were being portrayed as unsafe.
 

The case of one physician who spoke out

One of the highest-profile cases of a physician speaking out and being removed from work during the pandemic is that of Ming Lin, MD, an emergency physician who lost a job he had held for 17 years at St. Joseph Medical Center, in Bellingham, Wash. Dr. Lin lost his job after he made a series of Facebook posts that criticized the hospital’s COVID-19 preparedness efforts.

In an interview, Dr. Lin discussed the details of his situation to a degree that rarely occurs in such cases. This is one of the most extensive interviews he has granted.
 

Postings on Facebook

Dr. Lin said that on the basis of an intense study of the virus at the onset of the pandemic, he developed many ideas as to what could be done to mitigate its spread. While working as a locum tenens physician on his time off, he could see how others dealt with COVID-19.

Dr. Lin said from past experiences he did not feel that he could present his ideas directly to administration and be heard, so he decided to air his ideas about how his hospital could handle COVID-19 on his Facebook page, which drew a large audience.

He said he was certain that hospital administrators were reading his posts. He said receptionists at this hospital were advised not to wear masks, evidently because it would alarm patients. Dr. Lin said he posted concerns about their safety and called for them to wear masks. Soon after, the hospital directed receptionists to wear masks.

Dr. Lin’s Facebook posts also criticized the hospital for taking what he felt was too long to get results on COVID-19 tests. “It was taking them up to 10 days to get test results, because samples were being sent to a lab in California,” he said. He suggested it would be faster to send samples to the University of Washington. Soon after, the hospital started sending samples there.

In just a couple of weeks, Dr. Lin said, he voiced almost a dozen concerns. Each time the hospital made changes in line with his recommendations. Although he didn’t get any direct acknowledgment from the hospital for his help, he said he felt he was making a positive impact.
 

How employers react to physicians who speak out

Physicians who speak out about conditions tend to deeply disturb administrators, said William P. Sullivan, DO, JD, an emergency physician and lawyer in Frankfort, Ill., who has written about physicians being terminated by hospitals.

“These physicians go to the news media or they use social media,” Dr. Sullivan said, “but hospital administrators don’t want the public to hear bad things about their hospital.”

Then the public might not come to the hospital, which is an administrator’s worst nightmare. Even if physicians think their criticisms are reasonable, administrators may still fear a resulting drop in patients.

Dr. Houston, for example, was helping her Mississippi hospital by collecting donations of N95 masks for nurses, but to administrators, it showed that the hospital did not have enough masks.

“It is not helpful to stoke fear and anxiety, even if the intent is sincere,” a spokesperson for the hospital said.
 

Administrator fires back

Dr. Lin’s posts were deeply concerning to Richard DeCarlo, chief operating officer of PeaceHealth, which runs St. Joseph Hospital. Mr. DeCarlo discussed his concerns in a video interview in April with the blogger Zubin Damania, MD, known as ZDoggMD.

Comments on Dr. Lin’s Facebook posts showed that people “were fearful to go to the hospital,” he told Dr. Damania. “They were concluding that they would need to drive to another hospital.”

Mr. DeCarlo said he was also unhappy that Dr. Lin did not directly contact administrators about his concerns. “He didn’t communicate with his medical director,” Mr. DeCarlo said in the interview. “The ED staff had been meeting three times a week with the chief medical officer to make sure they had everything they needed, but he only attended one of these meetings and didn’t ask any questions.”

Dr. Lin maintains he did ask questions at the first meeting but stopped attending because he felt he wasn’t being heeded. “I found their tone not very receptive,” he said.
 

Doctor allegedly offered “misinformation”

At the start of the pandemic, some hospitals made it clear what would happen to doctors who brought up lack of PPE or other problems to the media. For example, NYU Langone Medical Center in New York sent an email to staff warning that speaking to the media without permission “will be subject to disciplinary action, including termination.”

PeaceHealth took a different tack. “It’s not that we have a policy that says don’t ever talk to the media,” Mr. DeCarlo said in the ZDoggMD interview, but in Dr. Lin’s case, “what was at issue was the misinformation. His leader went to him and said, ‘Look, you’re posting things that aren’t accurate.’ ”

Dr. Lin disputes that he provided any misinformation. In the interview, Mr. DeCarlo cited just one example of alleged misinformation. He said Dr. Lin called for a tent outside the emergency department (ED) to protect patients entering the department from aerosol exposure to COVID-19. Mr. DeCarlo said the tent was not needed because fewer people were using the ED.

“To put it in an extreme way,” Mr. DeCarlo said of Dr. Lin’s posts, “it was like yelling fire in a theater where there is not a fire.”

Dr. Lin said the hospital did briefly erect a tent and then removed it, and he still insisted that a tent was a good idea. He added that Mr. DeCarlo never mentioned any of the other suggestions Dr. Lin made, nor did he state that the hospital adopted them.
 

Doctor gets a warning

Dr. Lin said that after he started posting his concerns, he got a call from the emergency department director who worked for TeamHealth, an emergency medicine staffing firm that contracted with PeaceHealth and employed Dr. Lin, too.

Dr. Lin said his immediate supervisor at TeamHealth told him the hospital was unhappy with his posts and that he should take them down and suggested he might be fired. Dr. Lin said the supervisor also asked him to apologize to the hospital administration for these posts, but he refused to do so.

“Retracting and apologizing was not only wrong but would have left me vulnerable to being terminated with no repercussions,” he said.

“At that point, I realized I had crossed the Rubicon,” Dr. Lin said. He thought he might well be fired, no matter what he did, so he took his story to The Seattle Times, which had a much wider platform than his Facebook page had.

Dr. Lin lost his job at St. Joseph a week after The Seattle Times story about him appeared. “About 10 minutes before my shift was supposed to start, I received a text message from TeamHealth saying that someone else would be taking the shift,” he said.

In a release, TeamHealth insisted Dr. Lin was not fired and that he was scheduled to be reassigned to work at other hospitals. Dr. Lin, however, said he was not told this at the time and that he found out later that the new assignment would involve a pay cut and a significant commute. He said he has not taken any new assignments from TeamHealth since he lost his job at St. Joseph.

Dr. Lin has filed a lawsuit against PeaceHealth, TeamHealth, and Mr. DeCarlo, asking for his job back and for an apology. He said he has not asked for any financial damages at this point.

Since leaving St. Joseph, Dr. Lin has been working as an administrator for the Indian Health Service in the upper plains states. He said he can do some of the work at home in Washington State, which allows him to be with his wife and three young children.

Dr. Lin no longer sees patients. “I feel I have lost my confidence as a clinician,” he said. “I’m not sure why, but I find it hard to make quick judgments when taking care of patients.”

He said many doctors have told him about their own troubles with speaking out, but they did not want to come forward and talk about it because they feared more repercussions.
 

Do doctors who speak out have any rights?

Because TeamHealth, Dr. Lin’s actual employer, asserts he was never actually terminated, Dr. Lin has not been able to appeal his case internally in accordance with due process, an option that allows doctors to get a fair hearing and to appeal decisions against them.

The American Academy of Emergency Medicine pointed out this problem. “Dr. Lin, as a member of the medical staff, is entitled to full due process and a fair hearing from his peers on the medical staff,” the academy said in a statement supporting him.

The Joint Commission, the hospital accreditor, requires that hospitals provide due process to doctors before they can be terminated. However, Dr. Sullivan said employers often make physicians waive their due process rights in the employment contract. “The result is that the employer can terminate doctors for no reason,” he said.

In the 2013 survey of emergency physicians, 62% reported that their employers could terminate them without full due process.

Dr. Weiss, the Maryland MD-JD, said that when he advises doctors on their contracts, he generally tells them to cross out the waiver language. The applicant, he says, may also tell the employer that the waivers are considered unethical by many physician professional societies. In some cases, he said, the hospital will back down.
 

Conclusion

To maintain quality of care, it is essential that physicians feel free to speak out about issues that concern them. They can improve their chances of being heard by working directly with management and attending meetings, but in some cases, management may be unwilling to listen.

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

In April 2020, hospitalist Samantha Houston, MD, lost her job at Baptist Memorial Hospital–North, in Oxford, Miss., after she publicly campaigned to get donations of N95 masks for nurses. Dr. Houston filed a lawsuit against the hospital, saying she was improperly fired for speaking out. The lawsuit has not yet gone to trial.

John Fedele/Getty Images

In January 2017, emergency physician Raymond Brovont, MD, was fired by EmCare, an emergency physician staffing company, after reporting understaffing at hospitals with which it contracted in the Kansas City, Mo., area. Dr. Brovont sued EmCare, and the company lost the case. In February 2019, it was ordered to pay him $13.1 million in damages.

These are just two of several cases in recent years in which physicians have spoken out about problems involving patient care and have been sanctioned. Other physicians who see problems choose to stay silent.

Doctors often hesitate to speak out because of the prospect of losing their jobs. A 2013 study of emergency physicians found that nearly 20% reported a possible or real threat to their employment if they expressed concerns about quality of care.

When physicians do not speak openly about important medical issues, the quality of care in their institutions suffers, said a coauthor of the study, Larry D. Weiss, MD, JD, a retired professor of emergency medicine at the University of Maryland, Baltimore.

“Physicians can’t effectively represent patients if they are always thinking they can get fired for what they say,” Dr. Weiss said. “If you don’t have protections like due process, which is often the case, you are less likely to speak out.”

The COVID-19 pandemic put to the test physicians’ ability to speak publicly about troublesome issues. In the first few weeks, health care facilities were struggling to obtain personal protective equipment (PPE) and to create policies that would keep patients and caregivers safe.

Physicians such as Dr. Houston took the initiative to make sure their institutions were taking the right steps against COVID-19 and found themselves at loggerheads with administrators who were concerned that their organizations were being portrayed as unsafe.
 

The case of one physician who spoke out

One of the highest-profile cases of a physician speaking out and being removed from work during the pandemic is that of Ming Lin, MD, an emergency physician who lost a job he had held for 17 years at St. Joseph Medical Center, in Bellingham, Wash. Dr. Lin lost his job after he made a series of Facebook posts that criticized the hospital’s COVID-19 preparedness efforts.

In an interview, Dr. Lin discussed the details of his situation to a degree that rarely occurs in such cases. This is one of the most extensive interviews he has granted.
 

Postings on Facebook

Dr. Lin said that on the basis of an intense study of the virus at the onset of the pandemic, he developed many ideas as to what could be done to mitigate its spread. While working as a locum tenens physician on his time off, he could see how others dealt with COVID-19.

Dr. Lin said from past experiences he did not feel that he could present his ideas directly to administration and be heard, so he decided to air his ideas about how his hospital could handle COVID-19 on his Facebook page, which drew a large audience.

He said he was certain that hospital administrators were reading his posts. He said receptionists at this hospital were advised not to wear masks, evidently because it would alarm patients. Dr. Lin said he posted concerns about their safety and called for them to wear masks. Soon after, the hospital directed receptionists to wear masks.

Dr. Lin’s Facebook posts also criticized the hospital for taking what he felt was too long to get results on COVID-19 tests. “It was taking them up to 10 days to get test results, because samples were being sent to a lab in California,” he said. He suggested it would be faster to send samples to the University of Washington. Soon after, the hospital started sending samples there.

In just a couple of weeks, Dr. Lin said, he voiced almost a dozen concerns. Each time the hospital made changes in line with his recommendations. Although he didn’t get any direct acknowledgment from the hospital for his help, he said he felt he was making a positive impact.
 

How employers react to physicians who speak out

Physicians who speak out about conditions tend to deeply disturb administrators, said William P. Sullivan, DO, JD, an emergency physician and lawyer in Frankfort, Ill., who has written about physicians being terminated by hospitals.

“These physicians go to the news media or they use social media,” Dr. Sullivan said, “but hospital administrators don’t want the public to hear bad things about their hospital.”

Then the public might not come to the hospital, which is an administrator’s worst nightmare. Even if physicians think their criticisms are reasonable, administrators may still fear a resulting drop in patients.

Dr. Houston, for example, was helping her Mississippi hospital by collecting donations of N95 masks for nurses, but to administrators, it showed that the hospital did not have enough masks.

“It is not helpful to stoke fear and anxiety, even if the intent is sincere,” a spokesperson for the hospital said.
 

Administrator fires back

Dr. Lin’s posts were deeply concerning to Richard DeCarlo, chief operating officer of PeaceHealth, which runs St. Joseph Hospital. Mr. DeCarlo discussed his concerns in a video interview in April with the blogger Zubin Damania, MD, known as ZDoggMD.

Comments on Dr. Lin’s Facebook posts showed that people “were fearful to go to the hospital,” he told Dr. Damania. “They were concluding that they would need to drive to another hospital.”

Mr. DeCarlo said he was also unhappy that Dr. Lin did not directly contact administrators about his concerns. “He didn’t communicate with his medical director,” Mr. DeCarlo said in the interview. “The ED staff had been meeting three times a week with the chief medical officer to make sure they had everything they needed, but he only attended one of these meetings and didn’t ask any questions.”

Dr. Lin maintains he did ask questions at the first meeting but stopped attending because he felt he wasn’t being heeded. “I found their tone not very receptive,” he said.
 

Doctor allegedly offered “misinformation”

At the start of the pandemic, some hospitals made it clear what would happen to doctors who brought up lack of PPE or other problems to the media. For example, NYU Langone Medical Center in New York sent an email to staff warning that speaking to the media without permission “will be subject to disciplinary action, including termination.”

PeaceHealth took a different tack. “It’s not that we have a policy that says don’t ever talk to the media,” Mr. DeCarlo said in the ZDoggMD interview, but in Dr. Lin’s case, “what was at issue was the misinformation. His leader went to him and said, ‘Look, you’re posting things that aren’t accurate.’ ”

Dr. Lin disputes that he provided any misinformation. In the interview, Mr. DeCarlo cited just one example of alleged misinformation. He said Dr. Lin called for a tent outside the emergency department (ED) to protect patients entering the department from aerosol exposure to COVID-19. Mr. DeCarlo said the tent was not needed because fewer people were using the ED.

“To put it in an extreme way,” Mr. DeCarlo said of Dr. Lin’s posts, “it was like yelling fire in a theater where there is not a fire.”

Dr. Lin said the hospital did briefly erect a tent and then removed it, and he still insisted that a tent was a good idea. He added that Mr. DeCarlo never mentioned any of the other suggestions Dr. Lin made, nor did he state that the hospital adopted them.
 

Doctor gets a warning

Dr. Lin said that after he started posting his concerns, he got a call from the emergency department director who worked for TeamHealth, an emergency medicine staffing firm that contracted with PeaceHealth and employed Dr. Lin, too.

Dr. Lin said his immediate supervisor at TeamHealth told him the hospital was unhappy with his posts and that he should take them down and suggested he might be fired. Dr. Lin said the supervisor also asked him to apologize to the hospital administration for these posts, but he refused to do so.

“Retracting and apologizing was not only wrong but would have left me vulnerable to being terminated with no repercussions,” he said.

“At that point, I realized I had crossed the Rubicon,” Dr. Lin said. He thought he might well be fired, no matter what he did, so he took his story to The Seattle Times, which had a much wider platform than his Facebook page had.

Dr. Lin lost his job at St. Joseph a week after The Seattle Times story about him appeared. “About 10 minutes before my shift was supposed to start, I received a text message from TeamHealth saying that someone else would be taking the shift,” he said.

In a release, TeamHealth insisted Dr. Lin was not fired and that he was scheduled to be reassigned to work at other hospitals. Dr. Lin, however, said he was not told this at the time and that he found out later that the new assignment would involve a pay cut and a significant commute. He said he has not taken any new assignments from TeamHealth since he lost his job at St. Joseph.

Dr. Lin has filed a lawsuit against PeaceHealth, TeamHealth, and Mr. DeCarlo, asking for his job back and for an apology. He said he has not asked for any financial damages at this point.

Since leaving St. Joseph, Dr. Lin has been working as an administrator for the Indian Health Service in the upper plains states. He said he can do some of the work at home in Washington State, which allows him to be with his wife and three young children.

Dr. Lin no longer sees patients. “I feel I have lost my confidence as a clinician,” he said. “I’m not sure why, but I find it hard to make quick judgments when taking care of patients.”

He said many doctors have told him about their own troubles with speaking out, but they did not want to come forward and talk about it because they feared more repercussions.
 

Do doctors who speak out have any rights?

Because TeamHealth, Dr. Lin’s actual employer, asserts he was never actually terminated, Dr. Lin has not been able to appeal his case internally in accordance with due process, an option that allows doctors to get a fair hearing and to appeal decisions against them.

The American Academy of Emergency Medicine pointed out this problem. “Dr. Lin, as a member of the medical staff, is entitled to full due process and a fair hearing from his peers on the medical staff,” the academy said in a statement supporting him.

The Joint Commission, the hospital accreditor, requires that hospitals provide due process to doctors before they can be terminated. However, Dr. Sullivan said employers often make physicians waive their due process rights in the employment contract. “The result is that the employer can terminate doctors for no reason,” he said.

In the 2013 survey of emergency physicians, 62% reported that their employers could terminate them without full due process.

Dr. Weiss, the Maryland MD-JD, said that when he advises doctors on their contracts, he generally tells them to cross out the waiver language. The applicant, he says, may also tell the employer that the waivers are considered unethical by many physician professional societies. In some cases, he said, the hospital will back down.
 

Conclusion

To maintain quality of care, it is essential that physicians feel free to speak out about issues that concern them. They can improve their chances of being heard by working directly with management and attending meetings, but in some cases, management may be unwilling to listen.

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

In April 2020, hospitalist Samantha Houston, MD, lost her job at Baptist Memorial Hospital–North, in Oxford, Miss., after she publicly campaigned to get donations of N95 masks for nurses. Dr. Houston filed a lawsuit against the hospital, saying she was improperly fired for speaking out. The lawsuit has not yet gone to trial.

John Fedele/Getty Images

In January 2017, emergency physician Raymond Brovont, MD, was fired by EmCare, an emergency physician staffing company, after reporting understaffing at hospitals with which it contracted in the Kansas City, Mo., area. Dr. Brovont sued EmCare, and the company lost the case. In February 2019, it was ordered to pay him $13.1 million in damages.

These are just two of several cases in recent years in which physicians have spoken out about problems involving patient care and have been sanctioned. Other physicians who see problems choose to stay silent.

Doctors often hesitate to speak out because of the prospect of losing their jobs. A 2013 study of emergency physicians found that nearly 20% reported a possible or real threat to their employment if they expressed concerns about quality of care.

When physicians do not speak openly about important medical issues, the quality of care in their institutions suffers, said a coauthor of the study, Larry D. Weiss, MD, JD, a retired professor of emergency medicine at the University of Maryland, Baltimore.

“Physicians can’t effectively represent patients if they are always thinking they can get fired for what they say,” Dr. Weiss said. “If you don’t have protections like due process, which is often the case, you are less likely to speak out.”

The COVID-19 pandemic put to the test physicians’ ability to speak publicly about troublesome issues. In the first few weeks, health care facilities were struggling to obtain personal protective equipment (PPE) and to create policies that would keep patients and caregivers safe.

Physicians such as Dr. Houston took the initiative to make sure their institutions were taking the right steps against COVID-19 and found themselves at loggerheads with administrators who were concerned that their organizations were being portrayed as unsafe.
 

The case of one physician who spoke out

One of the highest-profile cases of a physician speaking out and being removed from work during the pandemic is that of Ming Lin, MD, an emergency physician who lost a job he had held for 17 years at St. Joseph Medical Center, in Bellingham, Wash. Dr. Lin lost his job after he made a series of Facebook posts that criticized the hospital’s COVID-19 preparedness efforts.

In an interview, Dr. Lin discussed the details of his situation to a degree that rarely occurs in such cases. This is one of the most extensive interviews he has granted.
 

Postings on Facebook

Dr. Lin said that on the basis of an intense study of the virus at the onset of the pandemic, he developed many ideas as to what could be done to mitigate its spread. While working as a locum tenens physician on his time off, he could see how others dealt with COVID-19.

Dr. Lin said from past experiences he did not feel that he could present his ideas directly to administration and be heard, so he decided to air his ideas about how his hospital could handle COVID-19 on his Facebook page, which drew a large audience.

He said he was certain that hospital administrators were reading his posts. He said receptionists at this hospital were advised not to wear masks, evidently because it would alarm patients. Dr. Lin said he posted concerns about their safety and called for them to wear masks. Soon after, the hospital directed receptionists to wear masks.

Dr. Lin’s Facebook posts also criticized the hospital for taking what he felt was too long to get results on COVID-19 tests. “It was taking them up to 10 days to get test results, because samples were being sent to a lab in California,” he said. He suggested it would be faster to send samples to the University of Washington. Soon after, the hospital started sending samples there.

In just a couple of weeks, Dr. Lin said, he voiced almost a dozen concerns. Each time the hospital made changes in line with his recommendations. Although he didn’t get any direct acknowledgment from the hospital for his help, he said he felt he was making a positive impact.
 

How employers react to physicians who speak out

Physicians who speak out about conditions tend to deeply disturb administrators, said William P. Sullivan, DO, JD, an emergency physician and lawyer in Frankfort, Ill., who has written about physicians being terminated by hospitals.

“These physicians go to the news media or they use social media,” Dr. Sullivan said, “but hospital administrators don’t want the public to hear bad things about their hospital.”

Then the public might not come to the hospital, which is an administrator’s worst nightmare. Even if physicians think their criticisms are reasonable, administrators may still fear a resulting drop in patients.

Dr. Houston, for example, was helping her Mississippi hospital by collecting donations of N95 masks for nurses, but to administrators, it showed that the hospital did not have enough masks.

“It is not helpful to stoke fear and anxiety, even if the intent is sincere,” a spokesperson for the hospital said.
 

Administrator fires back

Dr. Lin’s posts were deeply concerning to Richard DeCarlo, chief operating officer of PeaceHealth, which runs St. Joseph Hospital. Mr. DeCarlo discussed his concerns in a video interview in April with the blogger Zubin Damania, MD, known as ZDoggMD.

Comments on Dr. Lin’s Facebook posts showed that people “were fearful to go to the hospital,” he told Dr. Damania. “They were concluding that they would need to drive to another hospital.”

Mr. DeCarlo said he was also unhappy that Dr. Lin did not directly contact administrators about his concerns. “He didn’t communicate with his medical director,” Mr. DeCarlo said in the interview. “The ED staff had been meeting three times a week with the chief medical officer to make sure they had everything they needed, but he only attended one of these meetings and didn’t ask any questions.”

Dr. Lin maintains he did ask questions at the first meeting but stopped attending because he felt he wasn’t being heeded. “I found their tone not very receptive,” he said.
 

Doctor allegedly offered “misinformation”

At the start of the pandemic, some hospitals made it clear what would happen to doctors who brought up lack of PPE or other problems to the media. For example, NYU Langone Medical Center in New York sent an email to staff warning that speaking to the media without permission “will be subject to disciplinary action, including termination.”

PeaceHealth took a different tack. “It’s not that we have a policy that says don’t ever talk to the media,” Mr. DeCarlo said in the ZDoggMD interview, but in Dr. Lin’s case, “what was at issue was the misinformation. His leader went to him and said, ‘Look, you’re posting things that aren’t accurate.’ ”

Dr. Lin disputes that he provided any misinformation. In the interview, Mr. DeCarlo cited just one example of alleged misinformation. He said Dr. Lin called for a tent outside the emergency department (ED) to protect patients entering the department from aerosol exposure to COVID-19. Mr. DeCarlo said the tent was not needed because fewer people were using the ED.

“To put it in an extreme way,” Mr. DeCarlo said of Dr. Lin’s posts, “it was like yelling fire in a theater where there is not a fire.”

Dr. Lin said the hospital did briefly erect a tent and then removed it, and he still insisted that a tent was a good idea. He added that Mr. DeCarlo never mentioned any of the other suggestions Dr. Lin made, nor did he state that the hospital adopted them.
 

Doctor gets a warning

Dr. Lin said that after he started posting his concerns, he got a call from the emergency department director who worked for TeamHealth, an emergency medicine staffing firm that contracted with PeaceHealth and employed Dr. Lin, too.

Dr. Lin said his immediate supervisor at TeamHealth told him the hospital was unhappy with his posts and that he should take them down and suggested he might be fired. Dr. Lin said the supervisor also asked him to apologize to the hospital administration for these posts, but he refused to do so.

“Retracting and apologizing was not only wrong but would have left me vulnerable to being terminated with no repercussions,” he said.

“At that point, I realized I had crossed the Rubicon,” Dr. Lin said. He thought he might well be fired, no matter what he did, so he took his story to The Seattle Times, which had a much wider platform than his Facebook page had.

Dr. Lin lost his job at St. Joseph a week after The Seattle Times story about him appeared. “About 10 minutes before my shift was supposed to start, I received a text message from TeamHealth saying that someone else would be taking the shift,” he said.

In a release, TeamHealth insisted Dr. Lin was not fired and that he was scheduled to be reassigned to work at other hospitals. Dr. Lin, however, said he was not told this at the time and that he found out later that the new assignment would involve a pay cut and a significant commute. He said he has not taken any new assignments from TeamHealth since he lost his job at St. Joseph.

Dr. Lin has filed a lawsuit against PeaceHealth, TeamHealth, and Mr. DeCarlo, asking for his job back and for an apology. He said he has not asked for any financial damages at this point.

Since leaving St. Joseph, Dr. Lin has been working as an administrator for the Indian Health Service in the upper plains states. He said he can do some of the work at home in Washington State, which allows him to be with his wife and three young children.

Dr. Lin no longer sees patients. “I feel I have lost my confidence as a clinician,” he said. “I’m not sure why, but I find it hard to make quick judgments when taking care of patients.”

He said many doctors have told him about their own troubles with speaking out, but they did not want to come forward and talk about it because they feared more repercussions.
 

Do doctors who speak out have any rights?

Because TeamHealth, Dr. Lin’s actual employer, asserts he was never actually terminated, Dr. Lin has not been able to appeal his case internally in accordance with due process, an option that allows doctors to get a fair hearing and to appeal decisions against them.

The American Academy of Emergency Medicine pointed out this problem. “Dr. Lin, as a member of the medical staff, is entitled to full due process and a fair hearing from his peers on the medical staff,” the academy said in a statement supporting him.

The Joint Commission, the hospital accreditor, requires that hospitals provide due process to doctors before they can be terminated. However, Dr. Sullivan said employers often make physicians waive their due process rights in the employment contract. “The result is that the employer can terminate doctors for no reason,” he said.

In the 2013 survey of emergency physicians, 62% reported that their employers could terminate them without full due process.

Dr. Weiss, the Maryland MD-JD, said that when he advises doctors on their contracts, he generally tells them to cross out the waiver language. The applicant, he says, may also tell the employer that the waivers are considered unethical by many physician professional societies. In some cases, he said, the hospital will back down.
 

Conclusion

To maintain quality of care, it is essential that physicians feel free to speak out about issues that concern them. They can improve their chances of being heard by working directly with management and attending meetings, but in some cases, management may be unwilling to listen.

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

A large study of adolescent soccer players in Michigan revealed key differences in concussion injury metrics among males and females, underscoring a need to develop sex-specific approaches to managing injury in the sport.

Sport-related concussion (SRC) is a specific concern in young female athletes, study authors Abigail C. Bretzin, PhD, and colleagues noted in their paper, which appears in JAMA Network Open. Previous surveillance studies on SRC at the high school and college level have reported higher rates of injury risk and longer recovery outcomes in female soccer athletes. Taking a deeper dive into these trends, the investigators explored whether sex-associated differences existed in SRC, addressing the mechanics, management, and recovery from SRC.

“This is an area that is remarkably underresearched,” William Stewart, MBChB, PhD, the study’s corresponding author, said in an interview. Prior studies of males and females have shown that female axons are thinner, with fewer microtubules or internal scaffolding than male axons. This potentially increases risk of shear injury in females. Limited research has also cited differences in concussion risk across the menstrual cycle in female athletes.
 

Reporting system targets four injury areas

The investigators conducted a high school injury surveillance project in 43,741 male and 39,637 female soccer athletes participating in the Michigan High School Athletic Association (MHSAA) Head Injury Reporting System. The study included students from 9th to 12th grade, spanning from the beginning of academic year 2016-2017 to the end of academic year 2018-2019. Since 2015, the state has mandated high schools to submit data to MHSAA.

MHSAA captures data on four categories: person-to-person contact, person-to-object contact, person-to-playing surface contact, or uncertain about cause of the event. Study outcomes included details regarding injury mechanism, immediate management, and return-to-play time for each documented SRC.

Investigators reported notable differences among male and female players. Documented SRC risk was 1.88 times higher among adolescent girls than boys across all academic years (RR, 1.88; 95% CI, 1.69-2.09; P < .001). They also cited inconsistencies in distribution of injury mechanisms among the sexes. Females were most likely to suffer injury from equipment contact such as heading a ball (41.9%), whereas male players commonly sustained SRC from contact with another player (48.4%). The authors suggested that “female soccer athletes have lower neck strength and girth, compared with male athletes, with these variables inversely associated with linear and rotational head acceleration after soccer ball heading.”

Boys had greater odds of immediate removal from play and but also returned to the sport 2 days sooner than girls. “The possibility exists, therefore, that this longer recovery time might, in part, be reflective of our observed differences in immediate care, in particular removal from play,” the authors wrote. Immediate removal from play was also more common in cases where an athletic trainer played a part in evaluating players for SRC.
 

Eliminating the one-size-fits-all approach

Current concussion management is based on a “one-size-fits-all” model, said Dr. Stewart. Male and female athletes are treated following a common concussion management protocol, covering concussion detection through to rehabilitation. “This model of management is based on research that is almost exclusively in male athletes.”

What the study showed is this one-size-fits-all approach may be flawed, letting down female athletes. “We should be pursuing more research in sex differences in concussion and, importantly, putting these into practice in sex-specific concussion management protocols,” he suggested.

Future studies should also look at the effects of athletic trainer employment on SRC metrics. “Although this was a large, statewide epidemiological study of reported SRC in adolescent soccer athletes, inclusive of high schools with and without access to athletic trainers, the Head Injury Reporting System did not include information on the whether there were athletic trainer services available at each school, including specific athletic training services for soccer,” wrote the investigators, in citing the study’s limitations.
 

Girls report symptoms more often

“The researchers are to be commended for taking a prospective approach to address this common observation in high school sports,” said Keith J. Loud, MD, MSc, FAAP, a sports pediatrician at Children’s Hospital at Dartmouth-Hitchcock in Manchester, N.H. The results are “entirely believable,” said Dr. Loud, who was not affiliated with the study. “We have long postulated differences in neurophysiology, neck strength, style of play, and tendency to report as explanations for the observation that girls in high school soccer are diagnosed with more concussions than boys.”

The findings suggest that boys play more aggressively, but sustain fewer concussions, he added. Girls in the meantime, are more likely to speak up about their injury.

“Concussion diagnosis still relies to a large degree on the athlete to report symptoms, which is one of our hypotheses as to why girls seem to sustain more concussions – they report symptoms more often. That could also be why they have a prolonged recovery,” offered Dr. Loud. A main limitation of this study is it can’t overcome this reporting bias.

Dr. Loud was also concerned that girls were less likely to be removed from game play, even though they apparently sustained more concussions. “Perhaps that is because their injuries are less obvious on the field, and they are diagnosed when reported after the games.”

Dr. Stewart reported receiving grants from The Football Association and National Health Service Research Scotland during the study. He also served as a nonremunerated member of the Fédération Internationale de Football Association Independent Football Concussion Advisory Group and the Football Association Expert Panel on Concussion and Head Injury in Football. None of the other authors had disclosures.

A large study of adolescent soccer players in Michigan revealed key differences in concussion injury metrics among males and females, underscoring a need to develop sex-specific approaches to managing injury in the sport.

Sport-related concussion (SRC) is a specific concern in young female athletes, study authors Abigail C. Bretzin, PhD, and colleagues noted in their paper, which appears in JAMA Network Open. Previous surveillance studies on SRC at the high school and college level have reported higher rates of injury risk and longer recovery outcomes in female soccer athletes. Taking a deeper dive into these trends, the investigators explored whether sex-associated differences existed in SRC, addressing the mechanics, management, and recovery from SRC.

“This is an area that is remarkably underresearched,” William Stewart, MBChB, PhD, the study’s corresponding author, said in an interview. Prior studies of males and females have shown that female axons are thinner, with fewer microtubules or internal scaffolding than male axons. This potentially increases risk of shear injury in females. Limited research has also cited differences in concussion risk across the menstrual cycle in female athletes.
 

Reporting system targets four injury areas

The investigators conducted a high school injury surveillance project in 43,741 male and 39,637 female soccer athletes participating in the Michigan High School Athletic Association (MHSAA) Head Injury Reporting System. The study included students from 9th to 12th grade, spanning from the beginning of academic year 2016-2017 to the end of academic year 2018-2019. Since 2015, the state has mandated high schools to submit data to MHSAA.

MHSAA captures data on four categories: person-to-person contact, person-to-object contact, person-to-playing surface contact, or uncertain about cause of the event. Study outcomes included details regarding injury mechanism, immediate management, and return-to-play time for each documented SRC.

Investigators reported notable differences among male and female players. Documented SRC risk was 1.88 times higher among adolescent girls than boys across all academic years (RR, 1.88; 95% CI, 1.69-2.09; P < .001). They also cited inconsistencies in distribution of injury mechanisms among the sexes. Females were most likely to suffer injury from equipment contact such as heading a ball (41.9%), whereas male players commonly sustained SRC from contact with another player (48.4%). The authors suggested that “female soccer athletes have lower neck strength and girth, compared with male athletes, with these variables inversely associated with linear and rotational head acceleration after soccer ball heading.”

Boys had greater odds of immediate removal from play and but also returned to the sport 2 days sooner than girls. “The possibility exists, therefore, that this longer recovery time might, in part, be reflective of our observed differences in immediate care, in particular removal from play,” the authors wrote. Immediate removal from play was also more common in cases where an athletic trainer played a part in evaluating players for SRC.
 

Eliminating the one-size-fits-all approach

Current concussion management is based on a “one-size-fits-all” model, said Dr. Stewart. Male and female athletes are treated following a common concussion management protocol, covering concussion detection through to rehabilitation. “This model of management is based on research that is almost exclusively in male athletes.”

What the study showed is this one-size-fits-all approach may be flawed, letting down female athletes. “We should be pursuing more research in sex differences in concussion and, importantly, putting these into practice in sex-specific concussion management protocols,” he suggested.

Future studies should also look at the effects of athletic trainer employment on SRC metrics. “Although this was a large, statewide epidemiological study of reported SRC in adolescent soccer athletes, inclusive of high schools with and without access to athletic trainers, the Head Injury Reporting System did not include information on the whether there were athletic trainer services available at each school, including specific athletic training services for soccer,” wrote the investigators, in citing the study’s limitations.
 

Girls report symptoms more often

“The researchers are to be commended for taking a prospective approach to address this common observation in high school sports,” said Keith J. Loud, MD, MSc, FAAP, a sports pediatrician at Children’s Hospital at Dartmouth-Hitchcock in Manchester, N.H. The results are “entirely believable,” said Dr. Loud, who was not affiliated with the study. “We have long postulated differences in neurophysiology, neck strength, style of play, and tendency to report as explanations for the observation that girls in high school soccer are diagnosed with more concussions than boys.”

The findings suggest that boys play more aggressively, but sustain fewer concussions, he added. Girls in the meantime, are more likely to speak up about their injury.

“Concussion diagnosis still relies to a large degree on the athlete to report symptoms, which is one of our hypotheses as to why girls seem to sustain more concussions – they report symptoms more often. That could also be why they have a prolonged recovery,” offered Dr. Loud. A main limitation of this study is it can’t overcome this reporting bias.

Dr. Loud was also concerned that girls were less likely to be removed from game play, even though they apparently sustained more concussions. “Perhaps that is because their injuries are less obvious on the field, and they are diagnosed when reported after the games.”

Dr. Stewart reported receiving grants from The Football Association and National Health Service Research Scotland during the study. He also served as a nonremunerated member of the Fédération Internationale de Football Association Independent Football Concussion Advisory Group and the Football Association Expert Panel on Concussion and Head Injury in Football. None of the other authors had disclosures.

A large study of adolescent soccer players in Michigan revealed key differences in concussion injury metrics among males and females, underscoring a need to develop sex-specific approaches to managing injury in the sport.

Sport-related concussion (SRC) is a specific concern in young female athletes, study authors Abigail C. Bretzin, PhD, and colleagues noted in their paper, which appears in JAMA Network Open. Previous surveillance studies on SRC at the high school and college level have reported higher rates of injury risk and longer recovery outcomes in female soccer athletes. Taking a deeper dive into these trends, the investigators explored whether sex-associated differences existed in SRC, addressing the mechanics, management, and recovery from SRC.

“This is an area that is remarkably underresearched,” William Stewart, MBChB, PhD, the study’s corresponding author, said in an interview. Prior studies of males and females have shown that female axons are thinner, with fewer microtubules or internal scaffolding than male axons. This potentially increases risk of shear injury in females. Limited research has also cited differences in concussion risk across the menstrual cycle in female athletes.
 

Reporting system targets four injury areas

The investigators conducted a high school injury surveillance project in 43,741 male and 39,637 female soccer athletes participating in the Michigan High School Athletic Association (MHSAA) Head Injury Reporting System. The study included students from 9th to 12th grade, spanning from the beginning of academic year 2016-2017 to the end of academic year 2018-2019. Since 2015, the state has mandated high schools to submit data to MHSAA.

MHSAA captures data on four categories: person-to-person contact, person-to-object contact, person-to-playing surface contact, or uncertain about cause of the event. Study outcomes included details regarding injury mechanism, immediate management, and return-to-play time for each documented SRC.

Investigators reported notable differences among male and female players. Documented SRC risk was 1.88 times higher among adolescent girls than boys across all academic years (RR, 1.88; 95% CI, 1.69-2.09; P < .001). They also cited inconsistencies in distribution of injury mechanisms among the sexes. Females were most likely to suffer injury from equipment contact such as heading a ball (41.9%), whereas male players commonly sustained SRC from contact with another player (48.4%). The authors suggested that “female soccer athletes have lower neck strength and girth, compared with male athletes, with these variables inversely associated with linear and rotational head acceleration after soccer ball heading.”

Boys had greater odds of immediate removal from play and but also returned to the sport 2 days sooner than girls. “The possibility exists, therefore, that this longer recovery time might, in part, be reflective of our observed differences in immediate care, in particular removal from play,” the authors wrote. Immediate removal from play was also more common in cases where an athletic trainer played a part in evaluating players for SRC.
 

Eliminating the one-size-fits-all approach

Current concussion management is based on a “one-size-fits-all” model, said Dr. Stewart. Male and female athletes are treated following a common concussion management protocol, covering concussion detection through to rehabilitation. “This model of management is based on research that is almost exclusively in male athletes.”

What the study showed is this one-size-fits-all approach may be flawed, letting down female athletes. “We should be pursuing more research in sex differences in concussion and, importantly, putting these into practice in sex-specific concussion management protocols,” he suggested.

Future studies should also look at the effects of athletic trainer employment on SRC metrics. “Although this was a large, statewide epidemiological study of reported SRC in adolescent soccer athletes, inclusive of high schools with and without access to athletic trainers, the Head Injury Reporting System did not include information on the whether there were athletic trainer services available at each school, including specific athletic training services for soccer,” wrote the investigators, in citing the study’s limitations.
 

Girls report symptoms more often

“The researchers are to be commended for taking a prospective approach to address this common observation in high school sports,” said Keith J. Loud, MD, MSc, FAAP, a sports pediatrician at Children’s Hospital at Dartmouth-Hitchcock in Manchester, N.H. The results are “entirely believable,” said Dr. Loud, who was not affiliated with the study. “We have long postulated differences in neurophysiology, neck strength, style of play, and tendency to report as explanations for the observation that girls in high school soccer are diagnosed with more concussions than boys.”

The findings suggest that boys play more aggressively, but sustain fewer concussions, he added. Girls in the meantime, are more likely to speak up about their injury.

“Concussion diagnosis still relies to a large degree on the athlete to report symptoms, which is one of our hypotheses as to why girls seem to sustain more concussions – they report symptoms more often. That could also be why they have a prolonged recovery,” offered Dr. Loud. A main limitation of this study is it can’t overcome this reporting bias.

Dr. Loud was also concerned that girls were less likely to be removed from game play, even though they apparently sustained more concussions. “Perhaps that is because their injuries are less obvious on the field, and they are diagnosed when reported after the games.”

Dr. Stewart reported receiving grants from The Football Association and National Health Service Research Scotland during the study. He also served as a nonremunerated member of the Fédération Internationale de Football Association Independent Football Concussion Advisory Group and the Football Association Expert Panel on Concussion and Head Injury in Football. None of the other authors had disclosures.

Some, perhaps many, previously unrecognized cases of atrial fibrillation (AF) will come to light in a screening program aimed at older asymptomatic adults. The key question is whether the challenges of such systematic but age-restricted AF screening in the community, with oral anticoagulation (OAC) offered to those found to have the arrhythmia, is worthwhile in preventing events such as death or stroke.
 

Now there is evidence supporting such a clinical benefit from a large, prospective, randomized trial. A screening program restricted to people 75 or 76 years of age in two Swedish communities, which called on them to use a handheld single-lead ECG system at home intermittently for 2 weeks, was followed by a slight drop in clinical events over about 7 years.

The 4% decline in risk (P = .045) in the STROKESTOP trial’s “intention-to-treat” (ITT) analysis yielded a number needed to treat of 91; that is, that many people had to be targeted by the screening program to prevent one primary-endpoint clinical event.

Those included ischemic stroke, systemic thromboembolism, hospitalization for severe bleeding, and death from any cause, investigators reported April 23 during the virtual European Heart Rhythm Association (EHRA) 2021 Congress.

If that benefit and its significance seem marginal, some secondary findings might be reassuring. Half the population of the target age in the two communities – 13,979 randomly selected people – were invited to join the trial and follow the screening protocol, comprising the ITT cohort. The other half, numbering 13,996, was not invited and served as control subjects.

However, only 51% of the ITT cohort accepted the invitation and participated in the trial; they represented the “as-treated” cohort, observed Emma Svennberg, MD, PhD, Karolinska Institute, Danderyd Hospital, Stockholm, who presented the analysis at the EHRA sessions.

The screening protocol identified untreated AF, whether previously known or unknown, in about 5% of the 7,165 as-treated screening participants; OAC was initiated in about three-fourths of those cases.

The as-treated group, on their own, benefited with a 24% drop in the prospectively defined secondary endpoint of ischemic stroke, compared with the entire control group.

The clinical benefit in the ITT population was “small but significant,” but over the same period in the as-treated cohort, there was a highly significant drop in risk for ischemic stroke, Dr. Svennberg said in an interview.

The trial’s lead message, she said, is that “screening for atrial fibrillation in an elderly population reduces the risk of death and ischemic stroke without increasing the risk of bleeding.”
 

Caveats: As-treated vs. ITT

But there are caveats that complicate interpretation of the trial and, Dr. Svennberg proposed, point to the importance of that interpretation of both the ITT and as-treated analyses.

“We detected significantly more atrial fibrillation in the group that was randomized to screening. A major strength of our study was that we referred all of those individuals for a structured follow-up within the study,” she said. “Although the focus of the follow-up was oral anticoagulant therapy, other risk factors were also assessed and managed, such as hypertension and diabetes.”

It’s possible that increased detection of AF followed by such structured management contributed to the observed benefit, Dr. Svennberg proposed.

However, the exclusion of those in the prespecified ITT population who declined to be screened or otherwise didn’t participate left an as-treated cohort that was healthier than the ITT population or the control group.

Indeed, the nonparticipating invitees were sicker, with significantly more diabetes, vascular disease, hypertension, and heart failure, and higher CHA2DS2VASc stroke risk scores than those who agreed to participate.

“We took a more difficult route in setting up this study, in that we identified all individuals aged 75 to 76 residing in our two regions and excluded no one,” Dr. Svennberg said in an interview. “That means even individuals with end-stage disease, severe dementia, bedridden in nursing homes, et cetera, were also randomized but perhaps not likely or eligible to participate.”

Therefore, some invitees were unable to join the study even as others might have declined “out of low interest” or other personal reasons, she said. “We believe that this mimics how a population-based screening program would be performed if done in our country.”

In the ITT analysis, screening successfully identified previously unknown or untreated cases of AF, which led to expanded OAC use and intensified risk-factor management, “which was key to a successful outcome.”

In the as-treated analysis, Dr. Svennberg said, “I think a combination of the intervention and the population being overall more healthy was driving the secondary endpoint.”
 

Systematic vs. opportunistic screening

Although “opportunistic screening in individuals aged 65 and older” is recommended by current European Society of Cardiology guidelines, systematic screening, such as that used in STROKESTOP, has a much weaker evidence base, observed Renate B. Schnabel, MD, PhD, University Heart & Vascular Center, Hamburg, Germany, as the invited discussant after the STROKESTOP presentation.

STROKESTOP “is one of the first studies, if not the first study,” to show a clinical benefit from screening for AF, Dr. Schnabel said.

Fewer-than-projected primary outcome events were seen during the trial, and event curves for screened and control participants didn’t start to separate until about 4 years into the study, she said. It therefore might take a long time for the screened elderly to realize the clinical benefits of screening.

Studies such as the recent SCREEN-AF and mSTOPS have amply shown that AF screening in the asymptomatic elderly can reveal previously unrecognized AF far more often than would be detected in routine practice, allowing them the opportunity to go on OAC. But the trials weren’t able to show whether the benefits of such management outweigh the risks or costs.

Indeed, on April 20, the U.S. Preventive Services Task Force (USPSTF) released a draft recommendation statement concluding that “the current evidence is insufficient to assess the balance of benefits and harms” associated with AF screening in asymptomatic people at least 50 years of age.

In STROKESTOP, however, benefit for the primary outcome reached significance in the prespecified ITT analysis and “appeared to be driven by the reduction in ischemic stroke incidence,” Dr. Schnabel said.

“The future guidelines have gained strong evidence to judge on systematic atrial fibrillation screening” as it was performed in the trial, she said. “How to implement atrial fibrillation screening, including systematic screening in health care systems across Europe and beyond, remains an open question.”
 

A randomized population

STROKESTOP considered all 75- and 76-year-olds living in Sweden’s Stockholm County (n = 23,888) and the Halland region (n = 4,880) and randomly assigned them to the ITT group or a control group, with stratification by sex, birth year, and geographic region. In both groups, 54.6% were female and the mean CHA2DS2VASc score was 3.5.

People assigned to the ITT cohort were invited to be screened and followed. Those who agreed to participate underwent a baseline ECG assessment to detect or rule out permanent AF. Guideline-based OAC and follow-up was offered to those found with the arrhythmia. Those in sinus rhythm with no history of AF used a handheld single-lead ECG recorder (Zenicor) for 30 seconds twice daily for 14 days.

Structured management, including OAC, was offered to anyone demonstrating sufficient AF, that is, at least one bout without p waves in one 30-second recording or at least two such episodes lasting 10-29 seconds during the 2-week screening period.

In the ITT analysis, the hazard ratio (HR) for the composite clinical primary endpoint was 0.96 (95% confidence interval, 0.920-0.999; P = .045), but in the as-treated analysis, the HR for ischemic stroke was 0.76 (95% CI, 0.68-0.87; P < .001).

“I believe that this will likely be generalizable to most countries’ elderly residents,” Dr. Svennberg said. “I think if we can find a significant difference in our elderly population in Sweden, most countries will be able to do so, or find even more significant results.”

That’s because “baseline detection of AF in Sweden is high,” she said, “so new detection is likely more difficult.” Also, in Sweden, “care can be sought without monetary concern, and prescriptions are provided at low costs to the patients.” Therefore, patients newly identified with AF, whether in studies or not, “would likely be started on therapy.”

It will be important to know whether the screening strategy is cost-effective, Dr. Schnabel said, because “the overall effect, with a hazard ratio of 0.96, is not too big, and costs incurred by systematic screening are comparatively high.”

STROKESTOP “now provides sound information for cost-effectiveness analyses, which to date have largely relied on assumptions.”

STROKESTOP was partially supported by Carl Bennet AB, Boehringer-Ingelheim, Bayer, Bristol-Meyers Squibb, and Pfizer. Dr. Svennberg disclosed receiving fees for lectures or consulting from Bayer, Bristol-Meyers Squibb, Pfizer, Boehringer-Ingelheim, Merck Sharp & Dohme, and Sanofi; and institutional grants from Roche Diagnostics and Carl Bennett Ltd.

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

Some, perhaps many, previously unrecognized cases of atrial fibrillation (AF) will come to light in a screening program aimed at older asymptomatic adults. The key question is whether the challenges of such systematic but age-restricted AF screening in the community, with oral anticoagulation (OAC) offered to those found to have the arrhythmia, is worthwhile in preventing events such as death or stroke.
 

Now there is evidence supporting such a clinical benefit from a large, prospective, randomized trial. A screening program restricted to people 75 or 76 years of age in two Swedish communities, which called on them to use a handheld single-lead ECG system at home intermittently for 2 weeks, was followed by a slight drop in clinical events over about 7 years.

The 4% decline in risk (P = .045) in the STROKESTOP trial’s “intention-to-treat” (ITT) analysis yielded a number needed to treat of 91; that is, that many people had to be targeted by the screening program to prevent one primary-endpoint clinical event.

Those included ischemic stroke, systemic thromboembolism, hospitalization for severe bleeding, and death from any cause, investigators reported April 23 during the virtual European Heart Rhythm Association (EHRA) 2021 Congress.

If that benefit and its significance seem marginal, some secondary findings might be reassuring. Half the population of the target age in the two communities – 13,979 randomly selected people – were invited to join the trial and follow the screening protocol, comprising the ITT cohort. The other half, numbering 13,996, was not invited and served as control subjects.

However, only 51% of the ITT cohort accepted the invitation and participated in the trial; they represented the “as-treated” cohort, observed Emma Svennberg, MD, PhD, Karolinska Institute, Danderyd Hospital, Stockholm, who presented the analysis at the EHRA sessions.

The screening protocol identified untreated AF, whether previously known or unknown, in about 5% of the 7,165 as-treated screening participants; OAC was initiated in about three-fourths of those cases.

The as-treated group, on their own, benefited with a 24% drop in the prospectively defined secondary endpoint of ischemic stroke, compared with the entire control group.

The clinical benefit in the ITT population was “small but significant,” but over the same period in the as-treated cohort, there was a highly significant drop in risk for ischemic stroke, Dr. Svennberg said in an interview.

The trial’s lead message, she said, is that “screening for atrial fibrillation in an elderly population reduces the risk of death and ischemic stroke without increasing the risk of bleeding.”
 

Caveats: As-treated vs. ITT

But there are caveats that complicate interpretation of the trial and, Dr. Svennberg proposed, point to the importance of that interpretation of both the ITT and as-treated analyses.

“We detected significantly more atrial fibrillation in the group that was randomized to screening. A major strength of our study was that we referred all of those individuals for a structured follow-up within the study,” she said. “Although the focus of the follow-up was oral anticoagulant therapy, other risk factors were also assessed and managed, such as hypertension and diabetes.”

It’s possible that increased detection of AF followed by such structured management contributed to the observed benefit, Dr. Svennberg proposed.

However, the exclusion of those in the prespecified ITT population who declined to be screened or otherwise didn’t participate left an as-treated cohort that was healthier than the ITT population or the control group.

Indeed, the nonparticipating invitees were sicker, with significantly more diabetes, vascular disease, hypertension, and heart failure, and higher CHA2DS2VASc stroke risk scores than those who agreed to participate.

“We took a more difficult route in setting up this study, in that we identified all individuals aged 75 to 76 residing in our two regions and excluded no one,” Dr. Svennberg said in an interview. “That means even individuals with end-stage disease, severe dementia, bedridden in nursing homes, et cetera, were also randomized but perhaps not likely or eligible to participate.”

Therefore, some invitees were unable to join the study even as others might have declined “out of low interest” or other personal reasons, she said. “We believe that this mimics how a population-based screening program would be performed if done in our country.”

In the ITT analysis, screening successfully identified previously unknown or untreated cases of AF, which led to expanded OAC use and intensified risk-factor management, “which was key to a successful outcome.”

In the as-treated analysis, Dr. Svennberg said, “I think a combination of the intervention and the population being overall more healthy was driving the secondary endpoint.”
 

Systematic vs. opportunistic screening

Although “opportunistic screening in individuals aged 65 and older” is recommended by current European Society of Cardiology guidelines, systematic screening, such as that used in STROKESTOP, has a much weaker evidence base, observed Renate B. Schnabel, MD, PhD, University Heart & Vascular Center, Hamburg, Germany, as the invited discussant after the STROKESTOP presentation.

STROKESTOP “is one of the first studies, if not the first study,” to show a clinical benefit from screening for AF, Dr. Schnabel said.

Fewer-than-projected primary outcome events were seen during the trial, and event curves for screened and control participants didn’t start to separate until about 4 years into the study, she said. It therefore might take a long time for the screened elderly to realize the clinical benefits of screening.

Studies such as the recent SCREEN-AF and mSTOPS have amply shown that AF screening in the asymptomatic elderly can reveal previously unrecognized AF far more often than would be detected in routine practice, allowing them the opportunity to go on OAC. But the trials weren’t able to show whether the benefits of such management outweigh the risks or costs.

Indeed, on April 20, the U.S. Preventive Services Task Force (USPSTF) released a draft recommendation statement concluding that “the current evidence is insufficient to assess the balance of benefits and harms” associated with AF screening in asymptomatic people at least 50 years of age.

In STROKESTOP, however, benefit for the primary outcome reached significance in the prespecified ITT analysis and “appeared to be driven by the reduction in ischemic stroke incidence,” Dr. Schnabel said.

“The future guidelines have gained strong evidence to judge on systematic atrial fibrillation screening” as it was performed in the trial, she said. “How to implement atrial fibrillation screening, including systematic screening in health care systems across Europe and beyond, remains an open question.”
 

A randomized population

STROKESTOP considered all 75- and 76-year-olds living in Sweden’s Stockholm County (n = 23,888) and the Halland region (n = 4,880) and randomly assigned them to the ITT group or a control group, with stratification by sex, birth year, and geographic region. In both groups, 54.6% were female and the mean CHA2DS2VASc score was 3.5.

People assigned to the ITT cohort were invited to be screened and followed. Those who agreed to participate underwent a baseline ECG assessment to detect or rule out permanent AF. Guideline-based OAC and follow-up was offered to those found with the arrhythmia. Those in sinus rhythm with no history of AF used a handheld single-lead ECG recorder (Zenicor) for 30 seconds twice daily for 14 days.

Structured management, including OAC, was offered to anyone demonstrating sufficient AF, that is, at least one bout without p waves in one 30-second recording or at least two such episodes lasting 10-29 seconds during the 2-week screening period.

In the ITT analysis, the hazard ratio (HR) for the composite clinical primary endpoint was 0.96 (95% confidence interval, 0.920-0.999; P = .045), but in the as-treated analysis, the HR for ischemic stroke was 0.76 (95% CI, 0.68-0.87; P < .001).

“I believe that this will likely be generalizable to most countries’ elderly residents,” Dr. Svennberg said. “I think if we can find a significant difference in our elderly population in Sweden, most countries will be able to do so, or find even more significant results.”

That’s because “baseline detection of AF in Sweden is high,” she said, “so new detection is likely more difficult.” Also, in Sweden, “care can be sought without monetary concern, and prescriptions are provided at low costs to the patients.” Therefore, patients newly identified with AF, whether in studies or not, “would likely be started on therapy.”

It will be important to know whether the screening strategy is cost-effective, Dr. Schnabel said, because “the overall effect, with a hazard ratio of 0.96, is not too big, and costs incurred by systematic screening are comparatively high.”

STROKESTOP “now provides sound information for cost-effectiveness analyses, which to date have largely relied on assumptions.”

STROKESTOP was partially supported by Carl Bennet AB, Boehringer-Ingelheim, Bayer, Bristol-Meyers Squibb, and Pfizer. Dr. Svennberg disclosed receiving fees for lectures or consulting from Bayer, Bristol-Meyers Squibb, Pfizer, Boehringer-Ingelheim, Merck Sharp & Dohme, and Sanofi; and institutional grants from Roche Diagnostics and Carl Bennett Ltd.

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

Some, perhaps many, previously unrecognized cases of atrial fibrillation (AF) will come to light in a screening program aimed at older asymptomatic adults. The key question is whether the challenges of such systematic but age-restricted AF screening in the community, with oral anticoagulation (OAC) offered to those found to have the arrhythmia, is worthwhile in preventing events such as death or stroke.
 

Now there is evidence supporting such a clinical benefit from a large, prospective, randomized trial. A screening program restricted to people 75 or 76 years of age in two Swedish communities, which called on them to use a handheld single-lead ECG system at home intermittently for 2 weeks, was followed by a slight drop in clinical events over about 7 years.

The 4% decline in risk (P = .045) in the STROKESTOP trial’s “intention-to-treat” (ITT) analysis yielded a number needed to treat of 91; that is, that many people had to be targeted by the screening program to prevent one primary-endpoint clinical event.

Those included ischemic stroke, systemic thromboembolism, hospitalization for severe bleeding, and death from any cause, investigators reported April 23 during the virtual European Heart Rhythm Association (EHRA) 2021 Congress.

If that benefit and its significance seem marginal, some secondary findings might be reassuring. Half the population of the target age in the two communities – 13,979 randomly selected people – were invited to join the trial and follow the screening protocol, comprising the ITT cohort. The other half, numbering 13,996, was not invited and served as control subjects.

However, only 51% of the ITT cohort accepted the invitation and participated in the trial; they represented the “as-treated” cohort, observed Emma Svennberg, MD, PhD, Karolinska Institute, Danderyd Hospital, Stockholm, who presented the analysis at the EHRA sessions.

The screening protocol identified untreated AF, whether previously known or unknown, in about 5% of the 7,165 as-treated screening participants; OAC was initiated in about three-fourths of those cases.

The as-treated group, on their own, benefited with a 24% drop in the prospectively defined secondary endpoint of ischemic stroke, compared with the entire control group.

The clinical benefit in the ITT population was “small but significant,” but over the same period in the as-treated cohort, there was a highly significant drop in risk for ischemic stroke, Dr. Svennberg said in an interview.

The trial’s lead message, she said, is that “screening for atrial fibrillation in an elderly population reduces the risk of death and ischemic stroke without increasing the risk of bleeding.”
 

Caveats: As-treated vs. ITT

But there are caveats that complicate interpretation of the trial and, Dr. Svennberg proposed, point to the importance of that interpretation of both the ITT and as-treated analyses.

“We detected significantly more atrial fibrillation in the group that was randomized to screening. A major strength of our study was that we referred all of those individuals for a structured follow-up within the study,” she said. “Although the focus of the follow-up was oral anticoagulant therapy, other risk factors were also assessed and managed, such as hypertension and diabetes.”

It’s possible that increased detection of AF followed by such structured management contributed to the observed benefit, Dr. Svennberg proposed.

However, the exclusion of those in the prespecified ITT population who declined to be screened or otherwise didn’t participate left an as-treated cohort that was healthier than the ITT population or the control group.

Indeed, the nonparticipating invitees were sicker, with significantly more diabetes, vascular disease, hypertension, and heart failure, and higher CHA2DS2VASc stroke risk scores than those who agreed to participate.

“We took a more difficult route in setting up this study, in that we identified all individuals aged 75 to 76 residing in our two regions and excluded no one,” Dr. Svennberg said in an interview. “That means even individuals with end-stage disease, severe dementia, bedridden in nursing homes, et cetera, were also randomized but perhaps not likely or eligible to participate.”

Therefore, some invitees were unable to join the study even as others might have declined “out of low interest” or other personal reasons, she said. “We believe that this mimics how a population-based screening program would be performed if done in our country.”

In the ITT analysis, screening successfully identified previously unknown or untreated cases of AF, which led to expanded OAC use and intensified risk-factor management, “which was key to a successful outcome.”

In the as-treated analysis, Dr. Svennberg said, “I think a combination of the intervention and the population being overall more healthy was driving the secondary endpoint.”
 

Systematic vs. opportunistic screening

Although “opportunistic screening in individuals aged 65 and older” is recommended by current European Society of Cardiology guidelines, systematic screening, such as that used in STROKESTOP, has a much weaker evidence base, observed Renate B. Schnabel, MD, PhD, University Heart & Vascular Center, Hamburg, Germany, as the invited discussant after the STROKESTOP presentation.

STROKESTOP “is one of the first studies, if not the first study,” to show a clinical benefit from screening for AF, Dr. Schnabel said.

Fewer-than-projected primary outcome events were seen during the trial, and event curves for screened and control participants didn’t start to separate until about 4 years into the study, she said. It therefore might take a long time for the screened elderly to realize the clinical benefits of screening.

Studies such as the recent SCREEN-AF and mSTOPS have amply shown that AF screening in the asymptomatic elderly can reveal previously unrecognized AF far more often than would be detected in routine practice, allowing them the opportunity to go on OAC. But the trials weren’t able to show whether the benefits of such management outweigh the risks or costs.

Indeed, on April 20, the U.S. Preventive Services Task Force (USPSTF) released a draft recommendation statement concluding that “the current evidence is insufficient to assess the balance of benefits and harms” associated with AF screening in asymptomatic people at least 50 years of age.

In STROKESTOP, however, benefit for the primary outcome reached significance in the prespecified ITT analysis and “appeared to be driven by the reduction in ischemic stroke incidence,” Dr. Schnabel said.

“The future guidelines have gained strong evidence to judge on systematic atrial fibrillation screening” as it was performed in the trial, she said. “How to implement atrial fibrillation screening, including systematic screening in health care systems across Europe and beyond, remains an open question.”
 

A randomized population

STROKESTOP considered all 75- and 76-year-olds living in Sweden’s Stockholm County (n = 23,888) and the Halland region (n = 4,880) and randomly assigned them to the ITT group or a control group, with stratification by sex, birth year, and geographic region. In both groups, 54.6% were female and the mean CHA2DS2VASc score was 3.5.

People assigned to the ITT cohort were invited to be screened and followed. Those who agreed to participate underwent a baseline ECG assessment to detect or rule out permanent AF. Guideline-based OAC and follow-up was offered to those found with the arrhythmia. Those in sinus rhythm with no history of AF used a handheld single-lead ECG recorder (Zenicor) for 30 seconds twice daily for 14 days.

Structured management, including OAC, was offered to anyone demonstrating sufficient AF, that is, at least one bout without p waves in one 30-second recording or at least two such episodes lasting 10-29 seconds during the 2-week screening period.

In the ITT analysis, the hazard ratio (HR) for the composite clinical primary endpoint was 0.96 (95% confidence interval, 0.920-0.999; P = .045), but in the as-treated analysis, the HR for ischemic stroke was 0.76 (95% CI, 0.68-0.87; P < .001).

“I believe that this will likely be generalizable to most countries’ elderly residents,” Dr. Svennberg said. “I think if we can find a significant difference in our elderly population in Sweden, most countries will be able to do so, or find even more significant results.”

That’s because “baseline detection of AF in Sweden is high,” she said, “so new detection is likely more difficult.” Also, in Sweden, “care can be sought without monetary concern, and prescriptions are provided at low costs to the patients.” Therefore, patients newly identified with AF, whether in studies or not, “would likely be started on therapy.”

It will be important to know whether the screening strategy is cost-effective, Dr. Schnabel said, because “the overall effect, with a hazard ratio of 0.96, is not too big, and costs incurred by systematic screening are comparatively high.”

STROKESTOP “now provides sound information for cost-effectiveness analyses, which to date have largely relied on assumptions.”

STROKESTOP was partially supported by Carl Bennet AB, Boehringer-Ingelheim, Bayer, Bristol-Meyers Squibb, and Pfizer. Dr. Svennberg disclosed receiving fees for lectures or consulting from Bayer, Bristol-Meyers Squibb, Pfizer, Boehringer-Ingelheim, Merck Sharp & Dohme, and Sanofi; and institutional grants from Roche Diagnostics and Carl Bennett Ltd.

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