Neurology

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.

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.

On-call specialist incurred a clear ‘duty of care,’ court rules

An Illinois doctor who consulted with a patient’s treating physician but never actually saw the patient himself can’t escape a medical malpractice claim, a state appeals court ruled late in January.

The appeals decision is the result of a case involving the late Dennis Blagden.

On July 26, 2017, Mr. Blagden arrived at the Graham Hospital ED, in Canton, Ill., complaining of neck pain and an insect bite that had resulted in a swollen elbow. His ED doctor, Matthew McMillin, MD, who worked for Coleman Medical Associates, ordered tests and prescribed an anti-inflammatory pain medication and a muscle relaxant.

Dr. McMillin consulted via telephone with Kenneth Krock, MD, an internal medicine specialist and pediatrician, who was on call that day and who enjoyed admitting privileges at Graham. (Krock was also an employee of Coleman Medical Associates, which provided clinical staffing for the hospital.)

Dr. Krock had final admitting authority in this instance. Court records show that Dr. McMillin and he agreed that the patient could be discharged from the ED, despite Krock’s differential diagnosis indicating a possible infection.

Three days later, now with “hypercapnic respiratory failure, sepsis, and an altered mental state,” Mr. Blagden was again seen at the Graham Hospital ED. Mr. Blagden underwent intubation by Dr. McMillin, his original ED doctor, and was airlifted to Methodist Medical Center, in Peoria, 30 miles away. There, an MRI showed that he’d developed a spinal epidural abscess. On Aug. 7, 2017, a little over a week after his admission to Methodist, Mr. Blagden died from complications of his infection.

In January 2019, Mr. Blagden’s wife, Judy, filed a suit against Dr. McMillin, his practice, and Graham Hospital, which is a part of Graham Health System. Her suit alleged medical negligence in the death of her husband.

About 6 months later, Mr.s Blagden amended her original complaint, adding a second count of medical negligence against Dr. Krock; his practice and employer, Coleman Medical Associates; and Graham Hospital. In her amended complaint, Mrs. Blagden alleged that although Krock hadn’t actually seen her husband Dennis, his consultation with Dr. McMillin was sufficient to establish a doctor-patient relationship and thus a legal duty of care. That duty, Mrs. Blagden further alleged, was breached when Dr. Krock failed both to rule out her husband’s “infectious process” and to admit him for proper follow-up monitoring.

In July 2021, after the case had been transferred from Peoria County to Fulton County, Dr. Krock cried foul. In a motion to the court for summary judgment – that is, a ruling prior to an actual trial – he and his practice put forth the following argument: As a mere on-call consultant that day in 2017, he had neither seen the patient nor established a relationship with him, thereby precluding his legal duty of care.

The trial court judge agreed and granted both Dr. Krock and Dr. Coleman the summary judgment they had sought.

Mrs. Blagden then appealed to the Appellate Court of Illinois, Fourth District, which is located in Springfield.

In its unanimous decision, the three-judge panel reversed the lower court’s ruling. Taking direct aim at Dr. Krock’s earlier motion, Justice Eugene Doherty, who wrote the panel’s opinion, said that state law had long established that “the special relationship giving rise to a duty of care may exist even in the absence of any meeting between the physician and the patient where the physician performs specific services for the benefit of the patient.”

As Justice Doherty explained, Dr. Krock’s status that day as both the on-call doctor and the one with final admitting authority undermined his argument for summary judgment. Also undermining it, Justice Doherty added, was the fact that the conversation between the two doctors that day in 2017 was a formal exchange “contemplated by hospital bylaws.”

“While public policy should encourage informal consultations between physicians,” the justice continued, “it must not ignore actual physician involvement in decisions that directly affect a patient’s care.”

Following the Fourth District decision, the suit against Dr. McMillin, Dr. Krock, and the other defendants has now been tossed back to the trial court for further proceedings. At press time, no trial date had been set.
 

Will this proposed damages cap help retain more physicians?

Fear of a doctor shortage, triggered in part by a recent history of large payouts, has prompted Iowa lawmakers to push for new state caps on medical malpractice awards, as a story in the Des Moines Register reports.

Currently, Iowa caps most noneconomic damages – including those for pain and suffering – at $250,000, which is among the lowest such caps in the nation.

Under existing Iowa law, however, the limit doesn’t apply in extraordinary cases – that is, those involving “substantial or permanent loss of body function, substantial disfigurement, or death.” It also isn’t applicable in cases in which a jury decides that a defendant acted with intentional malice.

Lawmakers and Iowa Gov. Kim Reynolds would like to change this.

Under a Senate bill that has now passed out of committee and is awaiting debate on the Senate floor, even plaintiffs involved in extreme cases would receive no more than $1 million to compensate for their pain, suffering, or emotional distress. (The bill also includes a 2.1% annual hike to compensate for inflation. A similar bill, which adds “loss of pregnancy” to the list of extreme cases, has advanced to the House floor.)

Supporters say the proposed cap would help to limit mega awards. In Johnson County in March 2022, for instance, a jury awarded $97.4 million to the parents of a young boy who sustained severe brain injuries during his delivery, causing the clinic that had been involved in the case to file for bankruptcy. This award was nearly three times the total payouts ($35 million) in the entire state of Iowa in all of 2021, a year in which there were 192 closed claims, including at least a dozen that resulted in payouts of $1 million or more.

Supporters also think the proposed cap will mitigate what they see as a looming doctor shortage, especially among ob.gyns. in eastern Iowa. “I just cannot overstate how much this is affecting our workforce, and that turns into effects for the women and the children, the babies, in our state,” Shannon Leveridge, MD, an obstetrician in Davenport said. “In order to keep these women and their babies safe, we need doctors.”

But critics of the bill, including some lawmakers and the trial bar, say it overreaches, even in the case of the $97.4 million award.

“They don’t want to talk about the actual damages that are caused by medical negligence,” explained a spokesman for the trial lawyers. “So, you don’t hear about the fact that, of the $50 million of economic damages ... most of that is going to go to the 24/7 care for this child for the rest of his life.”

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

On-call specialist incurred a clear ‘duty of care,’ court rules

An Illinois doctor who consulted with a patient’s treating physician but never actually saw the patient himself can’t escape a medical malpractice claim, a state appeals court ruled late in January.

The appeals decision is the result of a case involving the late Dennis Blagden.

On July 26, 2017, Mr. Blagden arrived at the Graham Hospital ED, in Canton, Ill., complaining of neck pain and an insect bite that had resulted in a swollen elbow. His ED doctor, Matthew McMillin, MD, who worked for Coleman Medical Associates, ordered tests and prescribed an anti-inflammatory pain medication and a muscle relaxant.

Dr. McMillin consulted via telephone with Kenneth Krock, MD, an internal medicine specialist and pediatrician, who was on call that day and who enjoyed admitting privileges at Graham. (Krock was also an employee of Coleman Medical Associates, which provided clinical staffing for the hospital.)

Dr. Krock had final admitting authority in this instance. Court records show that Dr. McMillin and he agreed that the patient could be discharged from the ED, despite Krock’s differential diagnosis indicating a possible infection.

Three days later, now with “hypercapnic respiratory failure, sepsis, and an altered mental state,” Mr. Blagden was again seen at the Graham Hospital ED. Mr. Blagden underwent intubation by Dr. McMillin, his original ED doctor, and was airlifted to Methodist Medical Center, in Peoria, 30 miles away. There, an MRI showed that he’d developed a spinal epidural abscess. On Aug. 7, 2017, a little over a week after his admission to Methodist, Mr. Blagden died from complications of his infection.

In January 2019, Mr. Blagden’s wife, Judy, filed a suit against Dr. McMillin, his practice, and Graham Hospital, which is a part of Graham Health System. Her suit alleged medical negligence in the death of her husband.

About 6 months later, Mr.s Blagden amended her original complaint, adding a second count of medical negligence against Dr. Krock; his practice and employer, Coleman Medical Associates; and Graham Hospital. In her amended complaint, Mrs. Blagden alleged that although Krock hadn’t actually seen her husband Dennis, his consultation with Dr. McMillin was sufficient to establish a doctor-patient relationship and thus a legal duty of care. That duty, Mrs. Blagden further alleged, was breached when Dr. Krock failed both to rule out her husband’s “infectious process” and to admit him for proper follow-up monitoring.

In July 2021, after the case had been transferred from Peoria County to Fulton County, Dr. Krock cried foul. In a motion to the court for summary judgment – that is, a ruling prior to an actual trial – he and his practice put forth the following argument: As a mere on-call consultant that day in 2017, he had neither seen the patient nor established a relationship with him, thereby precluding his legal duty of care.

The trial court judge agreed and granted both Dr. Krock and Dr. Coleman the summary judgment they had sought.

Mrs. Blagden then appealed to the Appellate Court of Illinois, Fourth District, which is located in Springfield.

In its unanimous decision, the three-judge panel reversed the lower court’s ruling. Taking direct aim at Dr. Krock’s earlier motion, Justice Eugene Doherty, who wrote the panel’s opinion, said that state law had long established that “the special relationship giving rise to a duty of care may exist even in the absence of any meeting between the physician and the patient where the physician performs specific services for the benefit of the patient.”

As Justice Doherty explained, Dr. Krock’s status that day as both the on-call doctor and the one with final admitting authority undermined his argument for summary judgment. Also undermining it, Justice Doherty added, was the fact that the conversation between the two doctors that day in 2017 was a formal exchange “contemplated by hospital bylaws.”

“While public policy should encourage informal consultations between physicians,” the justice continued, “it must not ignore actual physician involvement in decisions that directly affect a patient’s care.”

Following the Fourth District decision, the suit against Dr. McMillin, Dr. Krock, and the other defendants has now been tossed back to the trial court for further proceedings. At press time, no trial date had been set.
 

Will this proposed damages cap help retain more physicians?

Fear of a doctor shortage, triggered in part by a recent history of large payouts, has prompted Iowa lawmakers to push for new state caps on medical malpractice awards, as a story in the Des Moines Register reports.

Currently, Iowa caps most noneconomic damages – including those for pain and suffering – at $250,000, which is among the lowest such caps in the nation.

Under existing Iowa law, however, the limit doesn’t apply in extraordinary cases – that is, those involving “substantial or permanent loss of body function, substantial disfigurement, or death.” It also isn’t applicable in cases in which a jury decides that a defendant acted with intentional malice.

Lawmakers and Iowa Gov. Kim Reynolds would like to change this.

Under a Senate bill that has now passed out of committee and is awaiting debate on the Senate floor, even plaintiffs involved in extreme cases would receive no more than $1 million to compensate for their pain, suffering, or emotional distress. (The bill also includes a 2.1% annual hike to compensate for inflation. A similar bill, which adds “loss of pregnancy” to the list of extreme cases, has advanced to the House floor.)

Supporters say the proposed cap would help to limit mega awards. In Johnson County in March 2022, for instance, a jury awarded $97.4 million to the parents of a young boy who sustained severe brain injuries during his delivery, causing the clinic that had been involved in the case to file for bankruptcy. This award was nearly three times the total payouts ($35 million) in the entire state of Iowa in all of 2021, a year in which there were 192 closed claims, including at least a dozen that resulted in payouts of $1 million or more.

Supporters also think the proposed cap will mitigate what they see as a looming doctor shortage, especially among ob.gyns. in eastern Iowa. “I just cannot overstate how much this is affecting our workforce, and that turns into effects for the women and the children, the babies, in our state,” Shannon Leveridge, MD, an obstetrician in Davenport said. “In order to keep these women and their babies safe, we need doctors.”

But critics of the bill, including some lawmakers and the trial bar, say it overreaches, even in the case of the $97.4 million award.

“They don’t want to talk about the actual damages that are caused by medical negligence,” explained a spokesman for the trial lawyers. “So, you don’t hear about the fact that, of the $50 million of economic damages ... most of that is going to go to the 24/7 care for this child for the rest of his life.”

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

On-call specialist incurred a clear ‘duty of care,’ court rules

An Illinois doctor who consulted with a patient’s treating physician but never actually saw the patient himself can’t escape a medical malpractice claim, a state appeals court ruled late in January.

The appeals decision is the result of a case involving the late Dennis Blagden.

On July 26, 2017, Mr. Blagden arrived at the Graham Hospital ED, in Canton, Ill., complaining of neck pain and an insect bite that had resulted in a swollen elbow. His ED doctor, Matthew McMillin, MD, who worked for Coleman Medical Associates, ordered tests and prescribed an anti-inflammatory pain medication and a muscle relaxant.

Dr. McMillin consulted via telephone with Kenneth Krock, MD, an internal medicine specialist and pediatrician, who was on call that day and who enjoyed admitting privileges at Graham. (Krock was also an employee of Coleman Medical Associates, which provided clinical staffing for the hospital.)

Dr. Krock had final admitting authority in this instance. Court records show that Dr. McMillin and he agreed that the patient could be discharged from the ED, despite Krock’s differential diagnosis indicating a possible infection.

Three days later, now with “hypercapnic respiratory failure, sepsis, and an altered mental state,” Mr. Blagden was again seen at the Graham Hospital ED. Mr. Blagden underwent intubation by Dr. McMillin, his original ED doctor, and was airlifted to Methodist Medical Center, in Peoria, 30 miles away. There, an MRI showed that he’d developed a spinal epidural abscess. On Aug. 7, 2017, a little over a week after his admission to Methodist, Mr. Blagden died from complications of his infection.

In January 2019, Mr. Blagden’s wife, Judy, filed a suit against Dr. McMillin, his practice, and Graham Hospital, which is a part of Graham Health System. Her suit alleged medical negligence in the death of her husband.

About 6 months later, Mr.s Blagden amended her original complaint, adding a second count of medical negligence against Dr. Krock; his practice and employer, Coleman Medical Associates; and Graham Hospital. In her amended complaint, Mrs. Blagden alleged that although Krock hadn’t actually seen her husband Dennis, his consultation with Dr. McMillin was sufficient to establish a doctor-patient relationship and thus a legal duty of care. That duty, Mrs. Blagden further alleged, was breached when Dr. Krock failed both to rule out her husband’s “infectious process” and to admit him for proper follow-up monitoring.

In July 2021, after the case had been transferred from Peoria County to Fulton County, Dr. Krock cried foul. In a motion to the court for summary judgment – that is, a ruling prior to an actual trial – he and his practice put forth the following argument: As a mere on-call consultant that day in 2017, he had neither seen the patient nor established a relationship with him, thereby precluding his legal duty of care.

The trial court judge agreed and granted both Dr. Krock and Dr. Coleman the summary judgment they had sought.

Mrs. Blagden then appealed to the Appellate Court of Illinois, Fourth District, which is located in Springfield.

In its unanimous decision, the three-judge panel reversed the lower court’s ruling. Taking direct aim at Dr. Krock’s earlier motion, Justice Eugene Doherty, who wrote the panel’s opinion, said that state law had long established that “the special relationship giving rise to a duty of care may exist even in the absence of any meeting between the physician and the patient where the physician performs specific services for the benefit of the patient.”

As Justice Doherty explained, Dr. Krock’s status that day as both the on-call doctor and the one with final admitting authority undermined his argument for summary judgment. Also undermining it, Justice Doherty added, was the fact that the conversation between the two doctors that day in 2017 was a formal exchange “contemplated by hospital bylaws.”

“While public policy should encourage informal consultations between physicians,” the justice continued, “it must not ignore actual physician involvement in decisions that directly affect a patient’s care.”

Following the Fourth District decision, the suit against Dr. McMillin, Dr. Krock, and the other defendants has now been tossed back to the trial court for further proceedings. At press time, no trial date had been set.
 

Will this proposed damages cap help retain more physicians?

Fear of a doctor shortage, triggered in part by a recent history of large payouts, has prompted Iowa lawmakers to push for new state caps on medical malpractice awards, as a story in the Des Moines Register reports.

Currently, Iowa caps most noneconomic damages – including those for pain and suffering – at $250,000, which is among the lowest such caps in the nation.

Under existing Iowa law, however, the limit doesn’t apply in extraordinary cases – that is, those involving “substantial or permanent loss of body function, substantial disfigurement, or death.” It also isn’t applicable in cases in which a jury decides that a defendant acted with intentional malice.

Lawmakers and Iowa Gov. Kim Reynolds would like to change this.

Under a Senate bill that has now passed out of committee and is awaiting debate on the Senate floor, even plaintiffs involved in extreme cases would receive no more than $1 million to compensate for their pain, suffering, or emotional distress. (The bill also includes a 2.1% annual hike to compensate for inflation. A similar bill, which adds “loss of pregnancy” to the list of extreme cases, has advanced to the House floor.)

Supporters say the proposed cap would help to limit mega awards. In Johnson County in March 2022, for instance, a jury awarded $97.4 million to the parents of a young boy who sustained severe brain injuries during his delivery, causing the clinic that had been involved in the case to file for bankruptcy. This award was nearly three times the total payouts ($35 million) in the entire state of Iowa in all of 2021, a year in which there were 192 closed claims, including at least a dozen that resulted in payouts of $1 million or more.

Supporters also think the proposed cap will mitigate what they see as a looming doctor shortage, especially among ob.gyns. in eastern Iowa. “I just cannot overstate how much this is affecting our workforce, and that turns into effects for the women and the children, the babies, in our state,” Shannon Leveridge, MD, an obstetrician in Davenport said. “In order to keep these women and their babies safe, we need doctors.”

But critics of the bill, including some lawmakers and the trial bar, say it overreaches, even in the case of the $97.4 million award.

“They don’t want to talk about the actual damages that are caused by medical negligence,” explained a spokesman for the trial lawyers. “So, you don’t hear about the fact that, of the $50 million of economic damages ... most of that is going to go to the 24/7 care for this child for the rest of his life.”

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

This transcript has been edited for clarity.

Hello. I’m Dr Sandra Fryhofer. Welcome to Medicine Matters. The topic is highlights from ACIP’s new adult schedule for 2023, published in the Annals of Internal Medicine, and why this new schedule may be a collector’s item.

It’s a new year, which means a new ACIP adult immunization schedule – a valuable resource collating ACIP’s most up-to-date vaccination recommendations.

Here are this year’s five most important changes:

• COVID vaccines now front and center
• New emphasis on polio vaccination
• Inclusion of some nonvaccine products (such as monoclonal antibody products)
• Pharmacists group has approved the schedule for the first time
• New shared clinical decision-making option for pneumococcal vaccines

The schedule’s organization remains the same. It still has four sections:

• Table 1: vaccinations by age
• Table 2: vaccinations by medical condition and other indications
• The Notes section (alphabetically ordered by vaccine type)
• Appendix listing of vaccine-specific contraindications and precautions

But what’s unique this year is that some of the abbreviations have historical implications. The first change is no big surprise in light of what we’ve gone through in the past few years. COVID vaccines are listed first on the cover page by brand name for those authorized and by company name for those still under US emergency use authorization. They’re also listed first on the graphics and in the notes.

COVID and mRNA and protein-based vaccines have now been assigned official abbreviations based on vaccine platform and valency.

• 1vCOV-mRNA: Comirnaty/Pfizer-BioNTech and Spikevax Moderna COVID-19 vaccines
• 2vCOV-mRNA: Pfizer-BioNTech and Moderna bivalent COVID-19 vaccines
• 1vCOV-aPS: Novavax COVID-19 vaccine

Also remarkable is the absence of COVID viral vector vaccines on the list. However, the viral vector COVID vaccine (which has been available but is not preferred) does have a CDC website link in the Notes section.

A sad but necessary inclusion was triggered by recent polio cases in New York. Polio was believed to be eradicated, and we thought adults no longer needed to be vaccinated against polio. In the new schedule, the polio vaccine is listed on the cover page but is not included in the tables. Current polio vaccination recommendations are now in the Notes section.

Also of historical significance and something that may set a precedent is the inclusion of nonvaccine products. The value of COVID preexposure prophylaxis with products including monoclonal antibodies (such as Evusheld) for people who are moderately or severely immunocompromised is mentioned in the Notes section.

For the first time ever, the schedule has been approved by the American Pharmacists Association, which validates pharmacists as established partners in vaccine administration.
 

Color-code key

One aspect of the schedule that has not changed is the color-code key:

• Yellow: Recommended if the patient meets the age requirement
• Purple: Indicated for those with additional risk factors or another indication
• Blue: Recommended based on shared clinical decision-making
• Orange: Precaution
• Red: Contraindicated or not recommended; the vaccine should not be administered. Overlays on the red more precisely clarify whether a vaccine is really contraindicated or just not recommended. An asterisk on red means vaccinate after pregnancy if indicated.
• Gray: No recommendation or not applicable

Vaccinations by age

Table 1 lists recommended vaccinations by age. There is one major change. COVID vaccines are on the first row of the graphic, with the need for both a primary series and boosters emphasized on the overlay. The notes have hyperlinks to the most up-to-date COVID vaccination recommendations.

Pneumococcal vaccination. Pneumococcal vaccination is routinely recommended starting at age 65. Current recommendations for those not previously vaccinated have not changed since last year. But on Table 1, the bottom half of the row for those 65 or older is now blue (and that’s new). This new color blue means shared clinical decision-making and applies to people who were previously considered fully vaccinated with the now extinct combination of PCV13 and PPSV23. These patients now have the option of getting a dose of PCV20 five years after completing their PCV13-PPSV23 combo series. This option is blue because the decision is up to you and your patient.

Check the notes for more pneumococcal vaccination details. For example, for those partially vaccinated using lower valency vaccines, there’s an option of substituting PCV20 for PPSV23 to broaden and increase durability of protection.

The pneumococcal vaccination recommendation options are complicated. A new pneumococcal vaccination app can help.

Hepatitis B. For adults under age 60, the color code for the hepatitis B vaccine is yellow, meaning it’s indicated for all. For older patients, the color code is purple. If a patient who is age 60 or older wants the hepatitis B vaccine, they can have it even in the absence of additional risk indications.
 

Vaccinations by medical condition or other indications

Other than a few minor word changes on the overlay, the only thing that’s new is the COVID vaccine row.

This table is helpful for matching vaccine recommendations with specific medical conditions, including pregnancy, immunocompromise, HIV (with specifics according to CD4 count), asplenia, complement deficiencies, heart disease, lung disease, alcoholism, chronic liver disease, diabetes, health care personnel, and men who have sex with men.

Use this table to dot the i’s and cross the t’s when it comes to vaccination recommendations. For example, take a look at the pregnancy column. Live virus vaccines, including LAIV, MMR, and varicella, are contraindicated and color-coded red. MMR and varicella also have an asterisk, meaning vaccinate after pregnancy if indicated. HPV vaccines are not live virus vaccines, but the overlay says they are not recommended during pregnancy. The asterisk indicates that you can vaccinate after pregnancy.
 

Vaccine notes

The notes are in alphabetical order, and their organization (routine, special situations, and shared clinical decision-making when indicated) has not changed. They are concise and succinct, but sometimes they’re not enough. That’s why vaccine-specific links to more complete recommendations are so convenient.

Notes for hepatitis B contain nuances on specific dosing for vaccinating patients on dialysis, as well as a reminder that newer hepatitis C vaccines such as Heplisav and PreHevbrio are not recommended during pregnancy due to lack of safety data.

For influenza, everyone 6 months or older still needs yearly flu vaccination with an age- and health-appropriate flu vaccine. But for those aged 65 or older, the notes specify the three vaccine versions now preferred: high-dose, recombinant, or adjuvanted versions. However, if these aren’t available, it’s better to get any flu vaccine than to go without.

Under meningococcal vaccines, the notes for MenACWY and MenB are combined. For MenB, trade names Bexsero and Trumenba are specified because the products are not interchangeable. Booster intervals for those still at risk are different for each vaccine type: every 5 years for MenACWY boosters, and every 2-3 years for boosts of MenB.

The recent polio cases in New York have put polio vaccination in the spotlight. ACIP has now reinstated its Polio Vaccine Work Group. The new schedule lists polio vaccines on the cover page. Current recommendations have been added to the notes section. Routine vaccination for adults is not necessary, at least for now. However, those at increased risk for exposure to polio fall in the special-situation category. For those at increased risk who have completed a polio vaccine series, a single lifetime IPV booster can be given. For those at increased risk who have not completed their polio vaccine series, now would be the time to finish the series.
 

Appendix

The final step in using the new schedule is checking the appendix and its list of vaccine-specific contraindications and precautions.

I hope this review of the new ACIP adult immunization schedule has been helpful. For Medicine Matters, I’m Dr. Sandra Fryhofer.

Dr. Fryhofer is clinical associate professor of medicine, Emory University, Atlanta. She reported numerous conflicts of interest.

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

This transcript has been edited for clarity.

Hello. I’m Dr Sandra Fryhofer. Welcome to Medicine Matters. The topic is highlights from ACIP’s new adult schedule for 2023, published in the Annals of Internal Medicine, and why this new schedule may be a collector’s item.

It’s a new year, which means a new ACIP adult immunization schedule – a valuable resource collating ACIP’s most up-to-date vaccination recommendations.

Here are this year’s five most important changes:

• COVID vaccines now front and center
• New emphasis on polio vaccination
• Inclusion of some nonvaccine products (such as monoclonal antibody products)
• Pharmacists group has approved the schedule for the first time
• New shared clinical decision-making option for pneumococcal vaccines

The schedule’s organization remains the same. It still has four sections:

• Table 1: vaccinations by age
• Table 2: vaccinations by medical condition and other indications
• The Notes section (alphabetically ordered by vaccine type)
• Appendix listing of vaccine-specific contraindications and precautions

But what’s unique this year is that some of the abbreviations have historical implications. The first change is no big surprise in light of what we’ve gone through in the past few years. COVID vaccines are listed first on the cover page by brand name for those authorized and by company name for those still under US emergency use authorization. They’re also listed first on the graphics and in the notes.

COVID and mRNA and protein-based vaccines have now been assigned official abbreviations based on vaccine platform and valency.

• 1vCOV-mRNA: Comirnaty/Pfizer-BioNTech and Spikevax Moderna COVID-19 vaccines
• 2vCOV-mRNA: Pfizer-BioNTech and Moderna bivalent COVID-19 vaccines
• 1vCOV-aPS: Novavax COVID-19 vaccine

Also remarkable is the absence of COVID viral vector vaccines on the list. However, the viral vector COVID vaccine (which has been available but is not preferred) does have a CDC website link in the Notes section.

A sad but necessary inclusion was triggered by recent polio cases in New York. Polio was believed to be eradicated, and we thought adults no longer needed to be vaccinated against polio. In the new schedule, the polio vaccine is listed on the cover page but is not included in the tables. Current polio vaccination recommendations are now in the Notes section.

Also of historical significance and something that may set a precedent is the inclusion of nonvaccine products. The value of COVID preexposure prophylaxis with products including monoclonal antibodies (such as Evusheld) for people who are moderately or severely immunocompromised is mentioned in the Notes section.

For the first time ever, the schedule has been approved by the American Pharmacists Association, which validates pharmacists as established partners in vaccine administration.
 

Color-code key

One aspect of the schedule that has not changed is the color-code key:

• Yellow: Recommended if the patient meets the age requirement
• Purple: Indicated for those with additional risk factors or another indication
• Blue: Recommended based on shared clinical decision-making
• Orange: Precaution
• Red: Contraindicated or not recommended; the vaccine should not be administered. Overlays on the red more precisely clarify whether a vaccine is really contraindicated or just not recommended. An asterisk on red means vaccinate after pregnancy if indicated.
• Gray: No recommendation or not applicable

Vaccinations by age

Table 1 lists recommended vaccinations by age. There is one major change. COVID vaccines are on the first row of the graphic, with the need for both a primary series and boosters emphasized on the overlay. The notes have hyperlinks to the most up-to-date COVID vaccination recommendations.

Pneumococcal vaccination. Pneumococcal vaccination is routinely recommended starting at age 65. Current recommendations for those not previously vaccinated have not changed since last year. But on Table 1, the bottom half of the row for those 65 or older is now blue (and that’s new). This new color blue means shared clinical decision-making and applies to people who were previously considered fully vaccinated with the now extinct combination of PCV13 and PPSV23. These patients now have the option of getting a dose of PCV20 five years after completing their PCV13-PPSV23 combo series. This option is blue because the decision is up to you and your patient.

Check the notes for more pneumococcal vaccination details. For example, for those partially vaccinated using lower valency vaccines, there’s an option of substituting PCV20 for PPSV23 to broaden and increase durability of protection.

The pneumococcal vaccination recommendation options are complicated. A new pneumococcal vaccination app can help.

Hepatitis B. For adults under age 60, the color code for the hepatitis B vaccine is yellow, meaning it’s indicated for all. For older patients, the color code is purple. If a patient who is age 60 or older wants the hepatitis B vaccine, they can have it even in the absence of additional risk indications.
 

Vaccinations by medical condition or other indications

Other than a few minor word changes on the overlay, the only thing that’s new is the COVID vaccine row.

This table is helpful for matching vaccine recommendations with specific medical conditions, including pregnancy, immunocompromise, HIV (with specifics according to CD4 count), asplenia, complement deficiencies, heart disease, lung disease, alcoholism, chronic liver disease, diabetes, health care personnel, and men who have sex with men.

Use this table to dot the i’s and cross the t’s when it comes to vaccination recommendations. For example, take a look at the pregnancy column. Live virus vaccines, including LAIV, MMR, and varicella, are contraindicated and color-coded red. MMR and varicella also have an asterisk, meaning vaccinate after pregnancy if indicated. HPV vaccines are not live virus vaccines, but the overlay says they are not recommended during pregnancy. The asterisk indicates that you can vaccinate after pregnancy.
 

Vaccine notes

The notes are in alphabetical order, and their organization (routine, special situations, and shared clinical decision-making when indicated) has not changed. They are concise and succinct, but sometimes they’re not enough. That’s why vaccine-specific links to more complete recommendations are so convenient.

Notes for hepatitis B contain nuances on specific dosing for vaccinating patients on dialysis, as well as a reminder that newer hepatitis C vaccines such as Heplisav and PreHevbrio are not recommended during pregnancy due to lack of safety data.

For influenza, everyone 6 months or older still needs yearly flu vaccination with an age- and health-appropriate flu vaccine. But for those aged 65 or older, the notes specify the three vaccine versions now preferred: high-dose, recombinant, or adjuvanted versions. However, if these aren’t available, it’s better to get any flu vaccine than to go without.

Under meningococcal vaccines, the notes for MenACWY and MenB are combined. For MenB, trade names Bexsero and Trumenba are specified because the products are not interchangeable. Booster intervals for those still at risk are different for each vaccine type: every 5 years for MenACWY boosters, and every 2-3 years for boosts of MenB.

The recent polio cases in New York have put polio vaccination in the spotlight. ACIP has now reinstated its Polio Vaccine Work Group. The new schedule lists polio vaccines on the cover page. Current recommendations have been added to the notes section. Routine vaccination for adults is not necessary, at least for now. However, those at increased risk for exposure to polio fall in the special-situation category. For those at increased risk who have completed a polio vaccine series, a single lifetime IPV booster can be given. For those at increased risk who have not completed their polio vaccine series, now would be the time to finish the series.
 

Appendix

The final step in using the new schedule is checking the appendix and its list of vaccine-specific contraindications and precautions.

I hope this review of the new ACIP adult immunization schedule has been helpful. For Medicine Matters, I’m Dr. Sandra Fryhofer.

Dr. Fryhofer is clinical associate professor of medicine, Emory University, Atlanta. She reported numerous conflicts of interest.

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

This transcript has been edited for clarity.

Hello. I’m Dr Sandra Fryhofer. Welcome to Medicine Matters. The topic is highlights from ACIP’s new adult schedule for 2023, published in the Annals of Internal Medicine, and why this new schedule may be a collector’s item.

It’s a new year, which means a new ACIP adult immunization schedule – a valuable resource collating ACIP’s most up-to-date vaccination recommendations.

Here are this year’s five most important changes:

• COVID vaccines now front and center
• New emphasis on polio vaccination
• Inclusion of some nonvaccine products (such as monoclonal antibody products)
• Pharmacists group has approved the schedule for the first time
• New shared clinical decision-making option for pneumococcal vaccines

The schedule’s organization remains the same. It still has four sections:

• Table 1: vaccinations by age
• Table 2: vaccinations by medical condition and other indications
• The Notes section (alphabetically ordered by vaccine type)
• Appendix listing of vaccine-specific contraindications and precautions

But what’s unique this year is that some of the abbreviations have historical implications. The first change is no big surprise in light of what we’ve gone through in the past few years. COVID vaccines are listed first on the cover page by brand name for those authorized and by company name for those still under US emergency use authorization. They’re also listed first on the graphics and in the notes.

COVID and mRNA and protein-based vaccines have now been assigned official abbreviations based on vaccine platform and valency.

• 1vCOV-mRNA: Comirnaty/Pfizer-BioNTech and Spikevax Moderna COVID-19 vaccines
• 2vCOV-mRNA: Pfizer-BioNTech and Moderna bivalent COVID-19 vaccines
• 1vCOV-aPS: Novavax COVID-19 vaccine

Also remarkable is the absence of COVID viral vector vaccines on the list. However, the viral vector COVID vaccine (which has been available but is not preferred) does have a CDC website link in the Notes section.

A sad but necessary inclusion was triggered by recent polio cases in New York. Polio was believed to be eradicated, and we thought adults no longer needed to be vaccinated against polio. In the new schedule, the polio vaccine is listed on the cover page but is not included in the tables. Current polio vaccination recommendations are now in the Notes section.

Also of historical significance and something that may set a precedent is the inclusion of nonvaccine products. The value of COVID preexposure prophylaxis with products including monoclonal antibodies (such as Evusheld) for people who are moderately or severely immunocompromised is mentioned in the Notes section.

For the first time ever, the schedule has been approved by the American Pharmacists Association, which validates pharmacists as established partners in vaccine administration.
 

Color-code key

One aspect of the schedule that has not changed is the color-code key:

• Yellow: Recommended if the patient meets the age requirement
• Purple: Indicated for those with additional risk factors or another indication
• Blue: Recommended based on shared clinical decision-making
• Orange: Precaution
• Red: Contraindicated or not recommended; the vaccine should not be administered. Overlays on the red more precisely clarify whether a vaccine is really contraindicated or just not recommended. An asterisk on red means vaccinate after pregnancy if indicated.
• Gray: No recommendation or not applicable

Vaccinations by age

Table 1 lists recommended vaccinations by age. There is one major change. COVID vaccines are on the first row of the graphic, with the need for both a primary series and boosters emphasized on the overlay. The notes have hyperlinks to the most up-to-date COVID vaccination recommendations.

Pneumococcal vaccination. Pneumococcal vaccination is routinely recommended starting at age 65. Current recommendations for those not previously vaccinated have not changed since last year. But on Table 1, the bottom half of the row for those 65 or older is now blue (and that’s new). This new color blue means shared clinical decision-making and applies to people who were previously considered fully vaccinated with the now extinct combination of PCV13 and PPSV23. These patients now have the option of getting a dose of PCV20 five years after completing their PCV13-PPSV23 combo series. This option is blue because the decision is up to you and your patient.

Check the notes for more pneumococcal vaccination details. For example, for those partially vaccinated using lower valency vaccines, there’s an option of substituting PCV20 for PPSV23 to broaden and increase durability of protection.

The pneumococcal vaccination recommendation options are complicated. A new pneumococcal vaccination app can help.

Hepatitis B. For adults under age 60, the color code for the hepatitis B vaccine is yellow, meaning it’s indicated for all. For older patients, the color code is purple. If a patient who is age 60 or older wants the hepatitis B vaccine, they can have it even in the absence of additional risk indications.
 

Vaccinations by medical condition or other indications

Other than a few minor word changes on the overlay, the only thing that’s new is the COVID vaccine row.

This table is helpful for matching vaccine recommendations with specific medical conditions, including pregnancy, immunocompromise, HIV (with specifics according to CD4 count), asplenia, complement deficiencies, heart disease, lung disease, alcoholism, chronic liver disease, diabetes, health care personnel, and men who have sex with men.

Use this table to dot the i’s and cross the t’s when it comes to vaccination recommendations. For example, take a look at the pregnancy column. Live virus vaccines, including LAIV, MMR, and varicella, are contraindicated and color-coded red. MMR and varicella also have an asterisk, meaning vaccinate after pregnancy if indicated. HPV vaccines are not live virus vaccines, but the overlay says they are not recommended during pregnancy. The asterisk indicates that you can vaccinate after pregnancy.
 

Vaccine notes

The notes are in alphabetical order, and their organization (routine, special situations, and shared clinical decision-making when indicated) has not changed. They are concise and succinct, but sometimes they’re not enough. That’s why vaccine-specific links to more complete recommendations are so convenient.

Notes for hepatitis B contain nuances on specific dosing for vaccinating patients on dialysis, as well as a reminder that newer hepatitis C vaccines such as Heplisav and PreHevbrio are not recommended during pregnancy due to lack of safety data.

For influenza, everyone 6 months or older still needs yearly flu vaccination with an age- and health-appropriate flu vaccine. But for those aged 65 or older, the notes specify the three vaccine versions now preferred: high-dose, recombinant, or adjuvanted versions. However, if these aren’t available, it’s better to get any flu vaccine than to go without.

Under meningococcal vaccines, the notes for MenACWY and MenB are combined. For MenB, trade names Bexsero and Trumenba are specified because the products are not interchangeable. Booster intervals for those still at risk are different for each vaccine type: every 5 years for MenACWY boosters, and every 2-3 years for boosts of MenB.

The recent polio cases in New York have put polio vaccination in the spotlight. ACIP has now reinstated its Polio Vaccine Work Group. The new schedule lists polio vaccines on the cover page. Current recommendations have been added to the notes section. Routine vaccination for adults is not necessary, at least for now. However, those at increased risk for exposure to polio fall in the special-situation category. For those at increased risk who have completed a polio vaccine series, a single lifetime IPV booster can be given. For those at increased risk who have not completed their polio vaccine series, now would be the time to finish the series.
 

Appendix

The final step in using the new schedule is checking the appendix and its list of vaccine-specific contraindications and precautions.

I hope this review of the new ACIP adult immunization schedule has been helpful. For Medicine Matters, I’m Dr. Sandra Fryhofer.

Dr. Fryhofer is clinical associate professor of medicine, Emory University, Atlanta. She reported numerous conflicts of interest.

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

Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature – our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.

Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature – our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.

Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature – our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.