Neurology Reviews

It’s amazing how many phone calls I get from different agencies and groups:

The Drug Enforcement Administration – A car rented in your name was found with fentanyl in the trunk.

The Maricopa County Sheriff’s Department – There is a warrant for your arrest due to failure to show up for jury duty and/or as an expert witness.

Doctors Without Borders – We treated one of your patients while they were overseas and need payment for the supplies used.

The Arizona Medical Board – Your license has been suspended.

The Department of Health & Human Services – Your patient database has been posted on the dark web.

Of course, any of these problems can be fixed simply paying the caller a fee by credit card, Bitcoin, or purchasing gift cards and reading off the numbers to them.

Really.

As you’ve probably guessed, none of these calls are real, they’re just popular scams that have been circulating among doctors’ (and other) offices for the last several years. You may have gotten some of them yourself.

I’m sure the vast majority of us don’t fall for them, but the scammer on the other end doesn’t care. All that the scammers need is one sucker to hit the jackpot.

And, realistically, that sucker could be any of us on a bad day. Timing is everything. If we’re frazzled by office events, or aware that the local medical board is looking into something, or have just been up all night at the hospital and are exhausted ... that’s when we’re most vulnerable, our razor’s edge is dull, our thought process slowed, and maybe at that moment we are just not as able to think clearly.

If I were younger I’d probably be more inclined to waste time messing around with them for the entertainment, trying to get them to give up on me after a while. But nowadays I have neither the time nor interest for that. In the rare cases that they make it past my secretary (which is pretty hard) I just hang up.

I’m not sure if it says more about us or them that this happens. I suppose doctors’ offices are the low-hanging fruit where they assume there’s money and (hopefully) someone who’s either gullible, not paying attention, or just not on top of things. As with any other business, if it weren’t profitable they wouldn’t do it. The best we can do is to make it as unprofitable as possible.

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

It’s amazing how many phone calls I get from different agencies and groups:

The Drug Enforcement Administration – A car rented in your name was found with fentanyl in the trunk.

The Maricopa County Sheriff’s Department – There is a warrant for your arrest due to failure to show up for jury duty and/or as an expert witness.

Doctors Without Borders – We treated one of your patients while they were overseas and need payment for the supplies used.

The Arizona Medical Board – Your license has been suspended.

The Department of Health & Human Services – Your patient database has been posted on the dark web.

Of course, any of these problems can be fixed simply paying the caller a fee by credit card, Bitcoin, or purchasing gift cards and reading off the numbers to them.

Really.

As you’ve probably guessed, none of these calls are real, they’re just popular scams that have been circulating among doctors’ (and other) offices for the last several years. You may have gotten some of them yourself.

I’m sure the vast majority of us don’t fall for them, but the scammer on the other end doesn’t care. All that the scammers need is one sucker to hit the jackpot.

And, realistically, that sucker could be any of us on a bad day. Timing is everything. If we’re frazzled by office events, or aware that the local medical board is looking into something, or have just been up all night at the hospital and are exhausted ... that’s when we’re most vulnerable, our razor’s edge is dull, our thought process slowed, and maybe at that moment we are just not as able to think clearly.

If I were younger I’d probably be more inclined to waste time messing around with them for the entertainment, trying to get them to give up on me after a while. But nowadays I have neither the time nor interest for that. In the rare cases that they make it past my secretary (which is pretty hard) I just hang up.

I’m not sure if it says more about us or them that this happens. I suppose doctors’ offices are the low-hanging fruit where they assume there’s money and (hopefully) someone who’s either gullible, not paying attention, or just not on top of things. As with any other business, if it weren’t profitable they wouldn’t do it. The best we can do is to make it as unprofitable as possible.

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

It’s amazing how many phone calls I get from different agencies and groups:

The Drug Enforcement Administration – A car rented in your name was found with fentanyl in the trunk.

The Maricopa County Sheriff’s Department – There is a warrant for your arrest due to failure to show up for jury duty and/or as an expert witness.

Doctors Without Borders – We treated one of your patients while they were overseas and need payment for the supplies used.

The Arizona Medical Board – Your license has been suspended.

The Department of Health & Human Services – Your patient database has been posted on the dark web.

Of course, any of these problems can be fixed simply paying the caller a fee by credit card, Bitcoin, or purchasing gift cards and reading off the numbers to them.

Really.

As you’ve probably guessed, none of these calls are real, they’re just popular scams that have been circulating among doctors’ (and other) offices for the last several years. You may have gotten some of them yourself.

I’m sure the vast majority of us don’t fall for them, but the scammer on the other end doesn’t care. All that the scammers need is one sucker to hit the jackpot.

And, realistically, that sucker could be any of us on a bad day. Timing is everything. If we’re frazzled by office events, or aware that the local medical board is looking into something, or have just been up all night at the hospital and are exhausted ... that’s when we’re most vulnerable, our razor’s edge is dull, our thought process slowed, and maybe at that moment we are just not as able to think clearly.

If I were younger I’d probably be more inclined to waste time messing around with them for the entertainment, trying to get them to give up on me after a while. But nowadays I have neither the time nor interest for that. In the rare cases that they make it past my secretary (which is pretty hard) I just hang up.

I’m not sure if it says more about us or them that this happens. I suppose doctors’ offices are the low-hanging fruit where they assume there’s money and (hopefully) someone who’s either gullible, not paying attention, or just not on top of things. As with any other business, if it weren’t profitable they wouldn’t do it. The best we can do is to make it as unprofitable as possible.

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

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

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

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

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

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

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

Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.

Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.

Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.

“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.

“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.

The study was published online in the American Journal of Psychiatry.
 

‘Toxic stressor’

Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.

Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.

Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.

Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.

Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.

The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”

“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.

“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
 

A consequence of toxic stress

This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.

The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.

In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”

These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
 

Social construct?

Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”

Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”

Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.

“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”

These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.

The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.

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

Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.

Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.

Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.

“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.

“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.

The study was published online in the American Journal of Psychiatry.
 

‘Toxic stressor’

Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.

Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.

Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.

Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.

Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.

The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”

“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.

“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
 

A consequence of toxic stress

This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.

The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.

In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”

These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
 

Social construct?

Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”

Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”

Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.

“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”

These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.

The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.

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

Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.

Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.

Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.

“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.

“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.

The study was published online in the American Journal of Psychiatry.
 

‘Toxic stressor’

Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.

Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.

Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.

Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.

Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.

The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”

“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.

“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
 

A consequence of toxic stress

This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.

The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.

In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”

These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
 

Social construct?

Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”

Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”

Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.

“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”

These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.

The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.

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

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

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

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

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

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

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

Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

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

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

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

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

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

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

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

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

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

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

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

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

In 2016, when Erin Schanning lost her brother Ethan to an overdose, she wanted to know what could have been done to have helped him. Ethan, who had struggled with opioids since getting a prescription for the drugs after a dental procedure in middle school, had tried dozens of treatments. But at the age of 30, he was gone.

“After my brother died, I started researching and was surprised to learn that there were many evidence-based ways to treat substance use disorder that he hadn’t had access to, even though he had doggedly pursued treatment,” Ms. Schanning told me in an interview. One of those treatments, buprenorphine, is one of the most effective tools that health care providers have to treat opioid use disorder. A partial opioid agonist, it reduces cravings and prevents overdose, decreasing mortality more effectively than almost any medication for any disease. Yet most providers have never prescribed it.

That may be about to change. Thanks largely to advocates such as Ms. Schanning, who founded End Substance Use Disorder after she lost her brother, Congress has finally removed barriers to prescribing buprenorphine. The special license to prescribe the medication, commonly known as the “X-waiver,” was officially eliminated as part of the passage of the Mainstreaming Addiction Treatment (MAT) Act. Immediately, following the passage of the Act, any provider with a DEA license became eligible to prescribe buprenorphine to treat opioid use disorder, and limits on the number of patients they could treat were eliminated.

Previously, buprenorphine, which has a better safety profile than almost any other prescription opioid because of its ceiling effect on respiratory depression,nonetheless required providers to obtain a special license to prescribe it, and – prior to an executive order from the Biden administration – 8 to 24 hours of training to do so. This led to a misconception that buprenorphine was dangerous, and created barriers for treatment during the worst overdose crisis in our country’s history. More than 110,00 overdose deaths occurred in 2021, representing a 468% increase in the last 2 decades.

Along with the MAT Act, the Medication Access and Training Expansion Act was passed in the same spending bill, requiring all prescribers who obtain a DEA license to do 8 hours of training on the treatment of substance use disorders. According to the Act, addiction specialty societies will have a role in creating trainings. Medical schools and residencies will also be able to fulfill this requirement with a “comprehensive” curriculum that covers all approved medications for the treatment of substance use disorders.

The DEA has not yet confirmed what training will be accepted, according to the Chief Medical Officer of the Substance Abuse and Mental Health Services Administration, Neeraj Gandotra, MD, who spoke to me in an interview. However, it is required to do so by April 5, 2023. Dr. Gandotra also emphasized that state and local laws, as well as insurance requirements, remain in place, and may place other constraints on prescribing. According to the Act, this new rule will be in effect by June 2023.

As an addiction medicine specialist and longtime buprenorphine prescriber, I am excited about these changes but wary of lingering resistance among health care providers. Will providers who have chosen not to get an X-waiver now look for another reason to not treat patients with substance use disorders?

Ms. Schanning remains hopeful. “I’m incredibly optimistic that health care providers are going to learn about buprenorphine and prescribe it to patients, and that patients are going to start asking about this medication,” she told me. “Seven in 10 providers say that they do feel an obligation to treat their patients with [opioid use disorder], but the federal government has made it very difficult to do so.”

Now with the X-waiver gone, providers and patients may be able to push for a long overdue shift in how we treat and conceptualize substance use disorders, she noted.

“Health care providers need to recognize substance use disorder as a medical condition that deserves treatment, and to speak about it like a medical condition,” Ms. Schanning said, by, for instance, moving away from using words such as “abuse” and “clean” and, instead, talking about treatable substance use disorders that can improve with evidence-based care, such as buprenorphine and methadone. “We also need to share stories of success and hope with people,” she added. “Once you’ve seen how someone can be transformed by treatment, it’s really difficult to say that substance use disorder is a character flaw, or their fault.”
 

A patient-centered approach

Over the past decade of practicing medicine, I have experienced this transformation personally. In residency, I believed that people had to be ready for help, to stop using, to change. I failed to recognize that many of those same people were asking me for help, and I wasn’t offering what they needed. The person who had to change was me.

As I moved toward a patient-centered approach, lowering barriers to starting and remaining in treatment, and collaborating with teams that could meet people wherever they might be, addictions became the most rewarding part of my practice.

I have never had more people thank me spontaneously and deeply for the care I provide. Plus, I have never seen a more profound change in the students I work with than when they witness someone with a substance use disorder offered treatment that works.

The X-waiver was not the only barrier to care, and the overdose crisis is not slowing down. But maybe with a new tool widely accessible, more of us will be ready to help.
 

Dr. Poorman is board certified in internal medicine and addiction medicine, assistant professor of medicine, University of Illinois at Chicago, and provides primary care and addiction services in Chicago. Her views do not necessarily reflect the views of her employer. She has reported no relevant disclosures, and she serves on the editorial advisory board of Internal Medicine News.

In 2016, when Erin Schanning lost her brother Ethan to an overdose, she wanted to know what could have been done to have helped him. Ethan, who had struggled with opioids since getting a prescription for the drugs after a dental procedure in middle school, had tried dozens of treatments. But at the age of 30, he was gone.

“After my brother died, I started researching and was surprised to learn that there were many evidence-based ways to treat substance use disorder that he hadn’t had access to, even though he had doggedly pursued treatment,” Ms. Schanning told me in an interview. One of those treatments, buprenorphine, is one of the most effective tools that health care providers have to treat opioid use disorder. A partial opioid agonist, it reduces cravings and prevents overdose, decreasing mortality more effectively than almost any medication for any disease. Yet most providers have never prescribed it.

That may be about to change. Thanks largely to advocates such as Ms. Schanning, who founded End Substance Use Disorder after she lost her brother, Congress has finally removed barriers to prescribing buprenorphine. The special license to prescribe the medication, commonly known as the “X-waiver,” was officially eliminated as part of the passage of the Mainstreaming Addiction Treatment (MAT) Act. Immediately, following the passage of the Act, any provider with a DEA license became eligible to prescribe buprenorphine to treat opioid use disorder, and limits on the number of patients they could treat were eliminated.

Previously, buprenorphine, which has a better safety profile than almost any other prescription opioid because of its ceiling effect on respiratory depression,nonetheless required providers to obtain a special license to prescribe it, and – prior to an executive order from the Biden administration – 8 to 24 hours of training to do so. This led to a misconception that buprenorphine was dangerous, and created barriers for treatment during the worst overdose crisis in our country’s history. More than 110,00 overdose deaths occurred in 2021, representing a 468% increase in the last 2 decades.

Along with the MAT Act, the Medication Access and Training Expansion Act was passed in the same spending bill, requiring all prescribers who obtain a DEA license to do 8 hours of training on the treatment of substance use disorders. According to the Act, addiction specialty societies will have a role in creating trainings. Medical schools and residencies will also be able to fulfill this requirement with a “comprehensive” curriculum that covers all approved medications for the treatment of substance use disorders.

The DEA has not yet confirmed what training will be accepted, according to the Chief Medical Officer of the Substance Abuse and Mental Health Services Administration, Neeraj Gandotra, MD, who spoke to me in an interview. However, it is required to do so by April 5, 2023. Dr. Gandotra also emphasized that state and local laws, as well as insurance requirements, remain in place, and may place other constraints on prescribing. According to the Act, this new rule will be in effect by June 2023.

As an addiction medicine specialist and longtime buprenorphine prescriber, I am excited about these changes but wary of lingering resistance among health care providers. Will providers who have chosen not to get an X-waiver now look for another reason to not treat patients with substance use disorders?

Ms. Schanning remains hopeful. “I’m incredibly optimistic that health care providers are going to learn about buprenorphine and prescribe it to patients, and that patients are going to start asking about this medication,” she told me. “Seven in 10 providers say that they do feel an obligation to treat their patients with [opioid use disorder], but the federal government has made it very difficult to do so.”

Now with the X-waiver gone, providers and patients may be able to push for a long overdue shift in how we treat and conceptualize substance use disorders, she noted.

“Health care providers need to recognize substance use disorder as a medical condition that deserves treatment, and to speak about it like a medical condition,” Ms. Schanning said, by, for instance, moving away from using words such as “abuse” and “clean” and, instead, talking about treatable substance use disorders that can improve with evidence-based care, such as buprenorphine and methadone. “We also need to share stories of success and hope with people,” she added. “Once you’ve seen how someone can be transformed by treatment, it’s really difficult to say that substance use disorder is a character flaw, or their fault.”
 

A patient-centered approach

Over the past decade of practicing medicine, I have experienced this transformation personally. In residency, I believed that people had to be ready for help, to stop using, to change. I failed to recognize that many of those same people were asking me for help, and I wasn’t offering what they needed. The person who had to change was me.

As I moved toward a patient-centered approach, lowering barriers to starting and remaining in treatment, and collaborating with teams that could meet people wherever they might be, addictions became the most rewarding part of my practice.

I have never had more people thank me spontaneously and deeply for the care I provide. Plus, I have never seen a more profound change in the students I work with than when they witness someone with a substance use disorder offered treatment that works.

The X-waiver was not the only barrier to care, and the overdose crisis is not slowing down. But maybe with a new tool widely accessible, more of us will be ready to help.
 

Dr. Poorman is board certified in internal medicine and addiction medicine, assistant professor of medicine, University of Illinois at Chicago, and provides primary care and addiction services in Chicago. Her views do not necessarily reflect the views of her employer. She has reported no relevant disclosures, and she serves on the editorial advisory board of Internal Medicine News.

In 2016, when Erin Schanning lost her brother Ethan to an overdose, she wanted to know what could have been done to have helped him. Ethan, who had struggled with opioids since getting a prescription for the drugs after a dental procedure in middle school, had tried dozens of treatments. But at the age of 30, he was gone.

“After my brother died, I started researching and was surprised to learn that there were many evidence-based ways to treat substance use disorder that he hadn’t had access to, even though he had doggedly pursued treatment,” Ms. Schanning told me in an interview. One of those treatments, buprenorphine, is one of the most effective tools that health care providers have to treat opioid use disorder. A partial opioid agonist, it reduces cravings and prevents overdose, decreasing mortality more effectively than almost any medication for any disease. Yet most providers have never prescribed it.

That may be about to change. Thanks largely to advocates such as Ms. Schanning, who founded End Substance Use Disorder after she lost her brother, Congress has finally removed barriers to prescribing buprenorphine. The special license to prescribe the medication, commonly known as the “X-waiver,” was officially eliminated as part of the passage of the Mainstreaming Addiction Treatment (MAT) Act. Immediately, following the passage of the Act, any provider with a DEA license became eligible to prescribe buprenorphine to treat opioid use disorder, and limits on the number of patients they could treat were eliminated.

Previously, buprenorphine, which has a better safety profile than almost any other prescription opioid because of its ceiling effect on respiratory depression,nonetheless required providers to obtain a special license to prescribe it, and – prior to an executive order from the Biden administration – 8 to 24 hours of training to do so. This led to a misconception that buprenorphine was dangerous, and created barriers for treatment during the worst overdose crisis in our country’s history. More than 110,00 overdose deaths occurred in 2021, representing a 468% increase in the last 2 decades.

Along with the MAT Act, the Medication Access and Training Expansion Act was passed in the same spending bill, requiring all prescribers who obtain a DEA license to do 8 hours of training on the treatment of substance use disorders. According to the Act, addiction specialty societies will have a role in creating trainings. Medical schools and residencies will also be able to fulfill this requirement with a “comprehensive” curriculum that covers all approved medications for the treatment of substance use disorders.

The DEA has not yet confirmed what training will be accepted, according to the Chief Medical Officer of the Substance Abuse and Mental Health Services Administration, Neeraj Gandotra, MD, who spoke to me in an interview. However, it is required to do so by April 5, 2023. Dr. Gandotra also emphasized that state and local laws, as well as insurance requirements, remain in place, and may place other constraints on prescribing. According to the Act, this new rule will be in effect by June 2023.

As an addiction medicine specialist and longtime buprenorphine prescriber, I am excited about these changes but wary of lingering resistance among health care providers. Will providers who have chosen not to get an X-waiver now look for another reason to not treat patients with substance use disorders?

Ms. Schanning remains hopeful. “I’m incredibly optimistic that health care providers are going to learn about buprenorphine and prescribe it to patients, and that patients are going to start asking about this medication,” she told me. “Seven in 10 providers say that they do feel an obligation to treat their patients with [opioid use disorder], but the federal government has made it very difficult to do so.”

Now with the X-waiver gone, providers and patients may be able to push for a long overdue shift in how we treat and conceptualize substance use disorders, she noted.

“Health care providers need to recognize substance use disorder as a medical condition that deserves treatment, and to speak about it like a medical condition,” Ms. Schanning said, by, for instance, moving away from using words such as “abuse” and “clean” and, instead, talking about treatable substance use disorders that can improve with evidence-based care, such as buprenorphine and methadone. “We also need to share stories of success and hope with people,” she added. “Once you’ve seen how someone can be transformed by treatment, it’s really difficult to say that substance use disorder is a character flaw, or their fault.”
 

A patient-centered approach

Over the past decade of practicing medicine, I have experienced this transformation personally. In residency, I believed that people had to be ready for help, to stop using, to change. I failed to recognize that many of those same people were asking me for help, and I wasn’t offering what they needed. The person who had to change was me.

As I moved toward a patient-centered approach, lowering barriers to starting and remaining in treatment, and collaborating with teams that could meet people wherever they might be, addictions became the most rewarding part of my practice.

I have never had more people thank me spontaneously and deeply for the care I provide. Plus, I have never seen a more profound change in the students I work with than when they witness someone with a substance use disorder offered treatment that works.

The X-waiver was not the only barrier to care, and the overdose crisis is not slowing down. But maybe with a new tool widely accessible, more of us will be ready to help.
 

Dr. Poorman is board certified in internal medicine and addiction medicine, assistant professor of medicine, University of Illinois at Chicago, and provides primary care and addiction services in Chicago. Her views do not necessarily reflect the views of her employer. She has reported no relevant disclosures, and she serves on the editorial advisory board of Internal Medicine News.

Drinking one or two cocktails a day may protect against dementia, while having three or more could increase risk, new research suggests.

Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.

Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.

But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.

“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.

“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.

The findings were published online in JAMA Network Open.


 

Tracking drinking habits

Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.

Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).

A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.

At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.

From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.

After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
 

Unexpected finding

Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.

Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).

Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.

Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.

But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.

“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.

However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.

Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.

“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
 

Risks persist

Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.

“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.

The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.

“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”

Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.

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

Drinking one or two cocktails a day may protect against dementia, while having three or more could increase risk, new research suggests.

Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.

Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.

But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.

“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.

“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.

The findings were published online in JAMA Network Open.


 

Tracking drinking habits

Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.

Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).

A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.

At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.

From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.

After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
 

Unexpected finding

Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.

Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).

Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.

Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.

But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.

“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.

However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.

Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.

“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
 

Risks persist

Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.

“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.

The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.

“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”

Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.

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

Drinking one or two cocktails a day may protect against dementia, while having three or more could increase risk, new research suggests.

Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.

Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.

But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.

“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.

“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.

The findings were published online in JAMA Network Open.


 

Tracking drinking habits

Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.

Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).

A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.

At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.

From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.

After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
 

Unexpected finding

Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.

Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).

Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.

Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.

But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.

“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.

However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.

Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.

“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
 

Risks persist

Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.

“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.

The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.

“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”

Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.

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