Pauline Anderson

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

Almost a third of patients with migraine have experienced some form of stigma, new research shows. Results from the OVERCOME population-based survey study, which included more than 59,000 respondents, showed about 32% reported experiencing migraine-related stigma “often” or “very often.”

Even those experiencing only a few headaches per month said they experienced negative attitudes from others about migraine.

“We have been utterly blind to the burden people with migraine experience in terms of how their disease is appreciated by others. It’s time to get busy and address this very stubborn social phenomenon,” said the study’s coinvestigator, Robert E. Shapiro, MD, PhD, professor emeritus, department of neurological sciences, Larner College of Medicine, University of Vermont, Burlington.

Population-based research

Stigma is defined as the discounting or discrediting of an individual with a trait that deviates from social norms. To date, there have been no significant population-based studies of how these attitudes affect individuals with migraine.

OVERCOME is a cross-sectional, longitudinal, prospective, web-based survey conducted in a representative sample of the United States population. For this new analysis, researchers pooled data from surveys conducted in 2018, 2019, and 2020.

The analysis included 59,004 respondents (mean age, 41.3 years; 75% women; 70% White) who reported one or more headache or migraine attacks during the previous 12 months and who met criteria for migraine from the International Classification of Headache Disorders. Among the patients, 35% had a college degree, and 89% suffered episodic-type headaches.

Researchers used the following four patient-reported outcome measures:

• Migraine Disability Assessment, which quantifies number of days missed at work, home, or social events over the previous 3 months
• Migraine Interictal Burden Scale–4, which measures burden of migraine between attacks over the previous 4 weeks
• Migraine-Specific Quality of Life Role-Function Restrictive, which assesses the functional effect of migraine on social and work-related activities over the previous 4 weeks
• Migraine-Related Stigma

For the latter, the investigators used two measures – the degree to which others think migraine is used to acquire secondary gain, such as avoiding commitments, and the degree to which others minimize the burden of migraine.
 

One of the most stigmatizing disorders

Results showed that 31.7% of participants reported experiencing stigmatization from one or both migraine-related stigma categories often or very often – a result Dr. Shapiro characterized as “pretty shocking.”

Participants with chronic headaches, defined as having 15 or more headache days per month, made up 11% of the sample. About 47% of these respondents felt stigma often or very often.

However, even 25% of participants with three or fewer headache days per month reported stigma.

“This is a fundamental tip that we are not really understanding the concerns that drive burden for people living with this disabling disease,” Dr. Shapiro said.

Some previous studies that compared levels of stigmatizing attitudes regarding various diseases showed that migraine is more stigmatized than even epilepsy, a condition “equated with demonic possession in biblical times,” he noted.

One study used machine learning to measure the number of pejorative or negative terms associated with various diseases. “Shockingly, migraine was one of the most stigmatized diseases,” said Dr. Shapiro. “It was as stigmatized as gonorrhea by certain measures.”

Results from the new study showed that, irrespective of the number of headache days experienced per month, there was a threefold increase in interictal burden among those reporting stigma often or very often, compared with those who didn’t report stigma.
 

Large impact on QoL

“Stigma is a social concept, so maybe it’s not surprising that it would be present whether or not someone is experiencing other symptoms of migraine,” said Dr. Shapiro.

Across all monthly headache days, experiencing more migraine-related stigma was associated with increased disability and decreased quality of life.

Dr. Shapiro noted that when it comes to migraine-specific quality of life, stigma appears to have more of an effect than number of headache days. “That means there are big gaps in our appreciation for what drives the burdens in the patient experience of living with this disabling disease,” he said.

He added that headache’s place within the migraine sphere needs to be reconsidered. “Its singular emphasis has limited our full appreciation of this disease and how we should be paying attention to the things that are important to patients,” he said.

Dr. Shapiro predicts that future clinical trials will include migraine-related stigma as a measure to guide trial enrollment.

In addition, researchers are now digging deeper to try to understand what factors are most likely to drive stigma. “We need to understand why those attitudes are held and who is more likely to hold those attitudes, and that may allow us to develop mitigating strategies to reduce those attitudes,” said Dr. Shapiro.
 

‘Worrisome’ findings

Commenting on the findings, Deborah Friedman, MD, professor, departments of neurology and of ophthalmology, UT Southwestern Medical Center, Dallas, said the data on stigma were “worrisome.”

Missing social occasions and lost productivity may make migraine more visible to others so perhaps may “provoke stigma or stigmatizing comments or stigmatizing attitudes,” said Dr. Friedman, who was not involved with the research.

She noted that patients with migraine might also have trouble functioning in the workplace. “They may not be able to tolerate the computer screen or smells of perfume at the office and not get accommodation for that,” she said.

In addition to external stigma, which was investigated in the study, individuals with migraine may also experience internal stigma – blaming themselves for their disease, which may make it less likely they will seek care, said Dr. Friedman.

“That’s a huge problem,” she added.

The OVERCOME study is funded by Lilly. Dr. Shapiro has been compensated by Lilly as a research consultant and as a member of the data monitoring committee for clinical trials for galcanezumab, a Lilly pharmaceutical. Dr. Friedman has reported no relevant financial relationships.

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

Almost a third of patients with migraine have experienced some form of stigma, new research shows. Results from the OVERCOME population-based survey study, which included more than 59,000 respondents, showed about 32% reported experiencing migraine-related stigma “often” or “very often.”

Even those experiencing only a few headaches per month said they experienced negative attitudes from others about migraine.

“We have been utterly blind to the burden people with migraine experience in terms of how their disease is appreciated by others. It’s time to get busy and address this very stubborn social phenomenon,” said the study’s coinvestigator, Robert E. Shapiro, MD, PhD, professor emeritus, department of neurological sciences, Larner College of Medicine, University of Vermont, Burlington.

Population-based research

Stigma is defined as the discounting or discrediting of an individual with a trait that deviates from social norms. To date, there have been no significant population-based studies of how these attitudes affect individuals with migraine.

OVERCOME is a cross-sectional, longitudinal, prospective, web-based survey conducted in a representative sample of the United States population. For this new analysis, researchers pooled data from surveys conducted in 2018, 2019, and 2020.

The analysis included 59,004 respondents (mean age, 41.3 years; 75% women; 70% White) who reported one or more headache or migraine attacks during the previous 12 months and who met criteria for migraine from the International Classification of Headache Disorders. Among the patients, 35% had a college degree, and 89% suffered episodic-type headaches.

Researchers used the following four patient-reported outcome measures:

• Migraine Disability Assessment, which quantifies number of days missed at work, home, or social events over the previous 3 months
• Migraine Interictal Burden Scale–4, which measures burden of migraine between attacks over the previous 4 weeks
• Migraine-Specific Quality of Life Role-Function Restrictive, which assesses the functional effect of migraine on social and work-related activities over the previous 4 weeks
• Migraine-Related Stigma

For the latter, the investigators used two measures – the degree to which others think migraine is used to acquire secondary gain, such as avoiding commitments, and the degree to which others minimize the burden of migraine.
 

One of the most stigmatizing disorders

Results showed that 31.7% of participants reported experiencing stigmatization from one or both migraine-related stigma categories often or very often – a result Dr. Shapiro characterized as “pretty shocking.”

Participants with chronic headaches, defined as having 15 or more headache days per month, made up 11% of the sample. About 47% of these respondents felt stigma often or very often.

However, even 25% of participants with three or fewer headache days per month reported stigma.

“This is a fundamental tip that we are not really understanding the concerns that drive burden for people living with this disabling disease,” Dr. Shapiro said.

Some previous studies that compared levels of stigmatizing attitudes regarding various diseases showed that migraine is more stigmatized than even epilepsy, a condition “equated with demonic possession in biblical times,” he noted.

One study used machine learning to measure the number of pejorative or negative terms associated with various diseases. “Shockingly, migraine was one of the most stigmatized diseases,” said Dr. Shapiro. “It was as stigmatized as gonorrhea by certain measures.”

Results from the new study showed that, irrespective of the number of headache days experienced per month, there was a threefold increase in interictal burden among those reporting stigma often or very often, compared with those who didn’t report stigma.
 

Large impact on QoL

“Stigma is a social concept, so maybe it’s not surprising that it would be present whether or not someone is experiencing other symptoms of migraine,” said Dr. Shapiro.

Across all monthly headache days, experiencing more migraine-related stigma was associated with increased disability and decreased quality of life.

Dr. Shapiro noted that when it comes to migraine-specific quality of life, stigma appears to have more of an effect than number of headache days. “That means there are big gaps in our appreciation for what drives the burdens in the patient experience of living with this disabling disease,” he said.

He added that headache’s place within the migraine sphere needs to be reconsidered. “Its singular emphasis has limited our full appreciation of this disease and how we should be paying attention to the things that are important to patients,” he said.

Dr. Shapiro predicts that future clinical trials will include migraine-related stigma as a measure to guide trial enrollment.

In addition, researchers are now digging deeper to try to understand what factors are most likely to drive stigma. “We need to understand why those attitudes are held and who is more likely to hold those attitudes, and that may allow us to develop mitigating strategies to reduce those attitudes,” said Dr. Shapiro.
 

‘Worrisome’ findings

Commenting on the findings, Deborah Friedman, MD, professor, departments of neurology and of ophthalmology, UT Southwestern Medical Center, Dallas, said the data on stigma were “worrisome.”

Missing social occasions and lost productivity may make migraine more visible to others so perhaps may “provoke stigma or stigmatizing comments or stigmatizing attitudes,” said Dr. Friedman, who was not involved with the research.

She noted that patients with migraine might also have trouble functioning in the workplace. “They may not be able to tolerate the computer screen or smells of perfume at the office and not get accommodation for that,” she said.

In addition to external stigma, which was investigated in the study, individuals with migraine may also experience internal stigma – blaming themselves for their disease, which may make it less likely they will seek care, said Dr. Friedman.

“That’s a huge problem,” she added.

The OVERCOME study is funded by Lilly. Dr. Shapiro has been compensated by Lilly as a research consultant and as a member of the data monitoring committee for clinical trials for galcanezumab, a Lilly pharmaceutical. Dr. Friedman has reported no relevant financial relationships.

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

Almost a third of patients with migraine have experienced some form of stigma, new research shows. Results from the OVERCOME population-based survey study, which included more than 59,000 respondents, showed about 32% reported experiencing migraine-related stigma “often” or “very often.”

Even those experiencing only a few headaches per month said they experienced negative attitudes from others about migraine.

“We have been utterly blind to the burden people with migraine experience in terms of how their disease is appreciated by others. It’s time to get busy and address this very stubborn social phenomenon,” said the study’s coinvestigator, Robert E. Shapiro, MD, PhD, professor emeritus, department of neurological sciences, Larner College of Medicine, University of Vermont, Burlington.

Population-based research

Stigma is defined as the discounting or discrediting of an individual with a trait that deviates from social norms. To date, there have been no significant population-based studies of how these attitudes affect individuals with migraine.

OVERCOME is a cross-sectional, longitudinal, prospective, web-based survey conducted in a representative sample of the United States population. For this new analysis, researchers pooled data from surveys conducted in 2018, 2019, and 2020.

The analysis included 59,004 respondents (mean age, 41.3 years; 75% women; 70% White) who reported one or more headache or migraine attacks during the previous 12 months and who met criteria for migraine from the International Classification of Headache Disorders. Among the patients, 35% had a college degree, and 89% suffered episodic-type headaches.

Researchers used the following four patient-reported outcome measures:

• Migraine Disability Assessment, which quantifies number of days missed at work, home, or social events over the previous 3 months
• Migraine Interictal Burden Scale–4, which measures burden of migraine between attacks over the previous 4 weeks
• Migraine-Specific Quality of Life Role-Function Restrictive, which assesses the functional effect of migraine on social and work-related activities over the previous 4 weeks
• Migraine-Related Stigma

For the latter, the investigators used two measures – the degree to which others think migraine is used to acquire secondary gain, such as avoiding commitments, and the degree to which others minimize the burden of migraine.
 

One of the most stigmatizing disorders

Results showed that 31.7% of participants reported experiencing stigmatization from one or both migraine-related stigma categories often or very often – a result Dr. Shapiro characterized as “pretty shocking.”

Participants with chronic headaches, defined as having 15 or more headache days per month, made up 11% of the sample. About 47% of these respondents felt stigma often or very often.

However, even 25% of participants with three or fewer headache days per month reported stigma.

“This is a fundamental tip that we are not really understanding the concerns that drive burden for people living with this disabling disease,” Dr. Shapiro said.

Some previous studies that compared levels of stigmatizing attitudes regarding various diseases showed that migraine is more stigmatized than even epilepsy, a condition “equated with demonic possession in biblical times,” he noted.

One study used machine learning to measure the number of pejorative or negative terms associated with various diseases. “Shockingly, migraine was one of the most stigmatized diseases,” said Dr. Shapiro. “It was as stigmatized as gonorrhea by certain measures.”

Results from the new study showed that, irrespective of the number of headache days experienced per month, there was a threefold increase in interictal burden among those reporting stigma often or very often, compared with those who didn’t report stigma.
 

Large impact on QoL

“Stigma is a social concept, so maybe it’s not surprising that it would be present whether or not someone is experiencing other symptoms of migraine,” said Dr. Shapiro.

Across all monthly headache days, experiencing more migraine-related stigma was associated with increased disability and decreased quality of life.

Dr. Shapiro noted that when it comes to migraine-specific quality of life, stigma appears to have more of an effect than number of headache days. “That means there are big gaps in our appreciation for what drives the burdens in the patient experience of living with this disabling disease,” he said.

He added that headache’s place within the migraine sphere needs to be reconsidered. “Its singular emphasis has limited our full appreciation of this disease and how we should be paying attention to the things that are important to patients,” he said.

Dr. Shapiro predicts that future clinical trials will include migraine-related stigma as a measure to guide trial enrollment.

In addition, researchers are now digging deeper to try to understand what factors are most likely to drive stigma. “We need to understand why those attitudes are held and who is more likely to hold those attitudes, and that may allow us to develop mitigating strategies to reduce those attitudes,” said Dr. Shapiro.
 

‘Worrisome’ findings

Commenting on the findings, Deborah Friedman, MD, professor, departments of neurology and of ophthalmology, UT Southwestern Medical Center, Dallas, said the data on stigma were “worrisome.”

Missing social occasions and lost productivity may make migraine more visible to others so perhaps may “provoke stigma or stigmatizing comments or stigmatizing attitudes,” said Dr. Friedman, who was not involved with the research.

She noted that patients with migraine might also have trouble functioning in the workplace. “They may not be able to tolerate the computer screen or smells of perfume at the office and not get accommodation for that,” she said.

In addition to external stigma, which was investigated in the study, individuals with migraine may also experience internal stigma – blaming themselves for their disease, which may make it less likely they will seek care, said Dr. Friedman.

“That’s a huge problem,” she added.

The OVERCOME study is funded by Lilly. Dr. Shapiro has been compensated by Lilly as a research consultant and as a member of the data monitoring committee for clinical trials for galcanezumab, a Lilly pharmaceutical. Dr. Friedman has reported no relevant financial relationships.

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

Crenezumab, an investigational medication designed to slow or prevent Alzheimer’s disease (AD), provides no cognitive benefit in patients at high genetic risk, new research suggests.

Top-line results for a phase 2 trial showed the novel drug, a monoclonal antibody designed to neutralize neurotoxic oligomers (a form of beta-amyloid), was not statistically superior to placebo in terms of cognitive ability or episodic memory function among cognitively unimpaired individuals with a genetic mutation for early-onset AD.

Genentech announced the negative results on June 16 together with Banner Alzheimer’s Institute, Phoenix.

During a press briefing, company representatives and researchers expressed disappointment with the initial results – but stressed numerous ongoing analyses have yet to be completed.

“This is the beginning of the story, but by no means the end of it,” Pierre N. Tariot, MD, director, Banner Alzheimer’s Institute, and one of the study leaders, said at the briefing.

API ADAD trial

The prospective, double-blind parallel-group Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease (ADAD) phase 2 trial enrolled 252 members of the world’s largest extended family with ADAD in Colombia. A total of 94% of the participants completed the study.

Two-thirds of participants carried the Presenilin 1 (PSEN1) E280A mutation, which virtually guarantees that carriers will develop AD at an average age of 44 years and dementia at an average age of 49 years.

Study participants were randomly assigned to receive crenezumab or placebo over a period of 5-8 years. The dose of crenezumab was increased at different time points during the trial as knowledge about potential treatment approaches for AD evolved.

Dr. Tariot noted the maximum dose was not provided for the entire treatment period. “The longest people received the highest dose was about 2 years,” he added.

Coprimary endpoints were rate of change in cognitive abilities, as measured by the API ADAD composite cognitive score, or episodic memory function, measured by the Free and Cued Selective Reminding Test Cueing Index.

Results showed these outcomes were not statistically significant for those receiving the active medication.

In addition to a range of cognitive measures, researchers also assessed amyloid PET and, later in the study, tau PET. MRI and cerebrospinal fluid (CSF) measures were also examined.

The investigators did find small numerical differences favoring crenezumab across the coprimary and multiple secondary and exploratory endpoints, but these were also not statistically significant.

Finally, no new safety issues were identified with crenezumab during the study.

Further analyses of data are ongoing and additional brain imaging and CSF biomarker results will be presented at the Alzheimer’s Association International Conference on Aug. 2.

While the study was not positive, it demonstrated that prevention trials are possible, even in less-than-ideal circumstances and generated a wealth of useful data, the investigators note.

“There were some differences between the treated and untreated patients, and we still need to understand which patients were most likely to experience those differences,” Rachelle Doody, MD, PhD, global head of neurodegeneration at Roche and Genentech, told briefing attendees.

“We need to understand the biomarkers involved and what [they’re] telling us about the disease and the timing of the intervention,” Dr. Doody said.

Prevention “needs to be one of our targeted therapeutic approaches but probably not our only one,” she added.

Beyond amyloid?

Commenting on the negative results, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said they demonstrate the need to focus beyond amyloid and more on the biology of aging.

“This broader approach coupled with advances in novel biomarkers is bringing us closer to the day when physicians will be able to zero in on the root causes of each patient’s Alzheimer’s – and tailor combinations of drug therapies to provide precision medicine,” Dr. Fillit, who was not involved with the research, said in statement.

Genentech is also evaluating the potential of gantenerumab for ADAD and for the prevention of sporadic AD and treatment of early Alzheimer’s in late-stage clinical trials. Results from the phase 3 GRADUATE studies of gantenerumab in early AD are expected by the end of the year.

The study was supported by the National Institute on Aging, contributions to Banner Alzheimer’s Foundation, and Genentech.

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

Crenezumab, an investigational medication designed to slow or prevent Alzheimer’s disease (AD), provides no cognitive benefit in patients at high genetic risk, new research suggests.

Top-line results for a phase 2 trial showed the novel drug, a monoclonal antibody designed to neutralize neurotoxic oligomers (a form of beta-amyloid), was not statistically superior to placebo in terms of cognitive ability or episodic memory function among cognitively unimpaired individuals with a genetic mutation for early-onset AD.

Genentech announced the negative results on June 16 together with Banner Alzheimer’s Institute, Phoenix.

During a press briefing, company representatives and researchers expressed disappointment with the initial results – but stressed numerous ongoing analyses have yet to be completed.

“This is the beginning of the story, but by no means the end of it,” Pierre N. Tariot, MD, director, Banner Alzheimer’s Institute, and one of the study leaders, said at the briefing.

API ADAD trial

The prospective, double-blind parallel-group Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease (ADAD) phase 2 trial enrolled 252 members of the world’s largest extended family with ADAD in Colombia. A total of 94% of the participants completed the study.

Two-thirds of participants carried the Presenilin 1 (PSEN1) E280A mutation, which virtually guarantees that carriers will develop AD at an average age of 44 years and dementia at an average age of 49 years.

Study participants were randomly assigned to receive crenezumab or placebo over a period of 5-8 years. The dose of crenezumab was increased at different time points during the trial as knowledge about potential treatment approaches for AD evolved.

Dr. Tariot noted the maximum dose was not provided for the entire treatment period. “The longest people received the highest dose was about 2 years,” he added.

Coprimary endpoints were rate of change in cognitive abilities, as measured by the API ADAD composite cognitive score, or episodic memory function, measured by the Free and Cued Selective Reminding Test Cueing Index.

Results showed these outcomes were not statistically significant for those receiving the active medication.

In addition to a range of cognitive measures, researchers also assessed amyloid PET and, later in the study, tau PET. MRI and cerebrospinal fluid (CSF) measures were also examined.

The investigators did find small numerical differences favoring crenezumab across the coprimary and multiple secondary and exploratory endpoints, but these were also not statistically significant.

Finally, no new safety issues were identified with crenezumab during the study.

Further analyses of data are ongoing and additional brain imaging and CSF biomarker results will be presented at the Alzheimer’s Association International Conference on Aug. 2.

While the study was not positive, it demonstrated that prevention trials are possible, even in less-than-ideal circumstances and generated a wealth of useful data, the investigators note.

“There were some differences between the treated and untreated patients, and we still need to understand which patients were most likely to experience those differences,” Rachelle Doody, MD, PhD, global head of neurodegeneration at Roche and Genentech, told briefing attendees.

“We need to understand the biomarkers involved and what [they’re] telling us about the disease and the timing of the intervention,” Dr. Doody said.

Prevention “needs to be one of our targeted therapeutic approaches but probably not our only one,” she added.

Beyond amyloid?

Commenting on the negative results, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said they demonstrate the need to focus beyond amyloid and more on the biology of aging.

“This broader approach coupled with advances in novel biomarkers is bringing us closer to the day when physicians will be able to zero in on the root causes of each patient’s Alzheimer’s – and tailor combinations of drug therapies to provide precision medicine,” Dr. Fillit, who was not involved with the research, said in statement.

Genentech is also evaluating the potential of gantenerumab for ADAD and for the prevention of sporadic AD and treatment of early Alzheimer’s in late-stage clinical trials. Results from the phase 3 GRADUATE studies of gantenerumab in early AD are expected by the end of the year.

The study was supported by the National Institute on Aging, contributions to Banner Alzheimer’s Foundation, and Genentech.

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

Crenezumab, an investigational medication designed to slow or prevent Alzheimer’s disease (AD), provides no cognitive benefit in patients at high genetic risk, new research suggests.

Top-line results for a phase 2 trial showed the novel drug, a monoclonal antibody designed to neutralize neurotoxic oligomers (a form of beta-amyloid), was not statistically superior to placebo in terms of cognitive ability or episodic memory function among cognitively unimpaired individuals with a genetic mutation for early-onset AD.

Genentech announced the negative results on June 16 together with Banner Alzheimer’s Institute, Phoenix.

During a press briefing, company representatives and researchers expressed disappointment with the initial results – but stressed numerous ongoing analyses have yet to be completed.

“This is the beginning of the story, but by no means the end of it,” Pierre N. Tariot, MD, director, Banner Alzheimer’s Institute, and one of the study leaders, said at the briefing.

API ADAD trial

The prospective, double-blind parallel-group Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease (ADAD) phase 2 trial enrolled 252 members of the world’s largest extended family with ADAD in Colombia. A total of 94% of the participants completed the study.

Two-thirds of participants carried the Presenilin 1 (PSEN1) E280A mutation, which virtually guarantees that carriers will develop AD at an average age of 44 years and dementia at an average age of 49 years.

Study participants were randomly assigned to receive crenezumab or placebo over a period of 5-8 years. The dose of crenezumab was increased at different time points during the trial as knowledge about potential treatment approaches for AD evolved.

Dr. Tariot noted the maximum dose was not provided for the entire treatment period. “The longest people received the highest dose was about 2 years,” he added.

Coprimary endpoints were rate of change in cognitive abilities, as measured by the API ADAD composite cognitive score, or episodic memory function, measured by the Free and Cued Selective Reminding Test Cueing Index.

Results showed these outcomes were not statistically significant for those receiving the active medication.

In addition to a range of cognitive measures, researchers also assessed amyloid PET and, later in the study, tau PET. MRI and cerebrospinal fluid (CSF) measures were also examined.

The investigators did find small numerical differences favoring crenezumab across the coprimary and multiple secondary and exploratory endpoints, but these were also not statistically significant.

Finally, no new safety issues were identified with crenezumab during the study.

Further analyses of data are ongoing and additional brain imaging and CSF biomarker results will be presented at the Alzheimer’s Association International Conference on Aug. 2.

While the study was not positive, it demonstrated that prevention trials are possible, even in less-than-ideal circumstances and generated a wealth of useful data, the investigators note.

“There were some differences between the treated and untreated patients, and we still need to understand which patients were most likely to experience those differences,” Rachelle Doody, MD, PhD, global head of neurodegeneration at Roche and Genentech, told briefing attendees.

“We need to understand the biomarkers involved and what [they’re] telling us about the disease and the timing of the intervention,” Dr. Doody said.

Prevention “needs to be one of our targeted therapeutic approaches but probably not our only one,” she added.

Beyond amyloid?

Commenting on the negative results, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said they demonstrate the need to focus beyond amyloid and more on the biology of aging.

“This broader approach coupled with advances in novel biomarkers is bringing us closer to the day when physicians will be able to zero in on the root causes of each patient’s Alzheimer’s – and tailor combinations of drug therapies to provide precision medicine,” Dr. Fillit, who was not involved with the research, said in statement.

Genentech is also evaluating the potential of gantenerumab for ADAD and for the prevention of sporadic AD and treatment of early Alzheimer’s in late-stage clinical trials. Results from the phase 3 GRADUATE studies of gantenerumab in early AD are expected by the end of the year.

The study was supported by the National Institute on Aging, contributions to Banner Alzheimer’s Foundation, and Genentech.

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

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

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

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

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

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

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

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

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

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

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

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

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

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

An opioid-centered curriculum for medical students improves awareness of pain management and treatment of opioid use disorder (OUD) and may help mitigate the current opioid crisis in the United States, new research suggests.

“Our study showed that implementing training for medical students about opioid use disorder and its treatment improves knowledge and understanding of clinical principles and may better prepare students to treat patients with this disorder,” study investigator Kimberly Hu, MD, psychiatry resident, Ohio State University, Columbus, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.

The U.S. opioid epidemic claims thousands of lives every year, and there’s evidence it’s getting worse, said Dr. Hu. U.S. data from December 2020 to December 2021 show opioid-related deaths increased by almost 15%.

In 2019, about 70% of the nearly 71,000 drug overdose deaths in the United States involved opioids and now it exceeds 100,000 per year, said Dr. Hu. She noted 80% of heroin users report their addiction started with prescription opioids, data that she described as “pretty staggering.”

Although treatments such as buprenorphine are available for OUD, “insufficient access to medications for opioid use disorder remains a significant barrier for patients,” said Dr. Hu.

“Training the next generation of physicians across all specialties is one way that we can work to improve access to care and improve the health and well-being of our patients.”

The study, which is ongoing, included 405 3rd-year medical students at Ohio State. Researchers provided these students with in-person or virtual (during the pandemic) training in buprenorphine prescribing and in-person clinical experience.

Dr. Hu and her colleagues tested the students before and after the intervention and estimated improvement in knowledge (score 0-23) and approach to clinical management principles (1-5).

The investigators found a statistically significant increase in overall knowledge (from a mean total score of 18.34 to 19.32; P < .001). There was also a statistically significant increase in self-reported understanding of clinical management principles related to screening for and treating OUDs (from a mean of 3.12 to a mean of 4.02; P < .001).

An additional evaluation survey was completed by 162 students at the end of the program. About 83% of these students said they knew how to manage acute pain, 62% felt they knew how to manage chronic pain, and 77% agreed they knew how to screen a patient for OUD.

Dr. Hu noted 3rd-year medical students are a little over halfway through medical school, after which they will go into residency in various specialties. Providing them with this knowledge early on allows them to incorporate it as they continue their training, she said.

“If they are able to screen their patients in any specialty they eventually choose to go into, then they can help link these patients to resources early and make sure there aren’t patients who are slipping through the cracks.”
 

Worthwhile, important research

Howard Liu, MD, chair of the department of psychiatry at the University of Nebraska Medical Center, Omaha, and incoming chair of the APA’s Council on Communications, applauded the study.

The proposed curriculum, he said, instills confidence in students and teaches important lessons they can apply no matter what field they choose.

Dr. Liu, who moderated a press briefing highlighting the study, noted every state is affected differently by the opioid epidemic, but the shortage of appropriate treatments for OUD is nationwide.

Commenting on the study, addiction specialist Elie G. Aoun, MD, of the division of law, medicine, and psychiatry at Columbia University, New York, said this research is “very worthwhile and important.”

He noted that attitudes about addiction need to change. When he taught medical students about substance use disorders, he was struck by some of their negative beliefs about addiction. For example, considering addicts as “junkies” who are “taking resources away” from what they perceive as more deserving patients.

Addiction has been ignored in medicine for too long, added Dr. Aoun. He noted the requirement for addiction training for psychiatry residents is 2 months while they spend 4 months learning internal medicine. “That makes no sense,” he said.

“And now with the opioid epidemic, we’re faced with the consequences of dismissing addiction for such a long time.”

A lack of understanding about addiction, and the “very limited number” of experienced people treating addictions, has contributed to the “huge problem” experts now face in treating addictions, said Dr. Aoun.

“So you want to approach this problem from as many different angles as you can.”

He praised the study for presenting “a framework to ‘medicalize’ the addiction model” for students. This, he said, will help them build empathy and see those with a substance use disorder as no different from other patients with medical conditions.

A curriculum such as the one presented by Dr. Hu and colleagues may spur more medical students into the addiction field, he said. “It may make them more willing to treat patients with addiction using evidence-based medicine rather than dismissing them.”

The study was supported by the Substance Abuse and Mental Health Services Administration.

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

An opioid-centered curriculum for medical students improves awareness of pain management and treatment of opioid use disorder (OUD) and may help mitigate the current opioid crisis in the United States, new research suggests.

“Our study showed that implementing training for medical students about opioid use disorder and its treatment improves knowledge and understanding of clinical principles and may better prepare students to treat patients with this disorder,” study investigator Kimberly Hu, MD, psychiatry resident, Ohio State University, Columbus, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.

The U.S. opioid epidemic claims thousands of lives every year, and there’s evidence it’s getting worse, said Dr. Hu. U.S. data from December 2020 to December 2021 show opioid-related deaths increased by almost 15%.

In 2019, about 70% of the nearly 71,000 drug overdose deaths in the United States involved opioids and now it exceeds 100,000 per year, said Dr. Hu. She noted 80% of heroin users report their addiction started with prescription opioids, data that she described as “pretty staggering.”

Although treatments such as buprenorphine are available for OUD, “insufficient access to medications for opioid use disorder remains a significant barrier for patients,” said Dr. Hu.

“Training the next generation of physicians across all specialties is one way that we can work to improve access to care and improve the health and well-being of our patients.”

The study, which is ongoing, included 405 3rd-year medical students at Ohio State. Researchers provided these students with in-person or virtual (during the pandemic) training in buprenorphine prescribing and in-person clinical experience.

Dr. Hu and her colleagues tested the students before and after the intervention and estimated improvement in knowledge (score 0-23) and approach to clinical management principles (1-5).

The investigators found a statistically significant increase in overall knowledge (from a mean total score of 18.34 to 19.32; P < .001). There was also a statistically significant increase in self-reported understanding of clinical management principles related to screening for and treating OUDs (from a mean of 3.12 to a mean of 4.02; P < .001).

An additional evaluation survey was completed by 162 students at the end of the program. About 83% of these students said they knew how to manage acute pain, 62% felt they knew how to manage chronic pain, and 77% agreed they knew how to screen a patient for OUD.

Dr. Hu noted 3rd-year medical students are a little over halfway through medical school, after which they will go into residency in various specialties. Providing them with this knowledge early on allows them to incorporate it as they continue their training, she said.

“If they are able to screen their patients in any specialty they eventually choose to go into, then they can help link these patients to resources early and make sure there aren’t patients who are slipping through the cracks.”
 

Worthwhile, important research

Howard Liu, MD, chair of the department of psychiatry at the University of Nebraska Medical Center, Omaha, and incoming chair of the APA’s Council on Communications, applauded the study.

The proposed curriculum, he said, instills confidence in students and teaches important lessons they can apply no matter what field they choose.

Dr. Liu, who moderated a press briefing highlighting the study, noted every state is affected differently by the opioid epidemic, but the shortage of appropriate treatments for OUD is nationwide.

Commenting on the study, addiction specialist Elie G. Aoun, MD, of the division of law, medicine, and psychiatry at Columbia University, New York, said this research is “very worthwhile and important.”

He noted that attitudes about addiction need to change. When he taught medical students about substance use disorders, he was struck by some of their negative beliefs about addiction. For example, considering addicts as “junkies” who are “taking resources away” from what they perceive as more deserving patients.

Addiction has been ignored in medicine for too long, added Dr. Aoun. He noted the requirement for addiction training for psychiatry residents is 2 months while they spend 4 months learning internal medicine. “That makes no sense,” he said.

“And now with the opioid epidemic, we’re faced with the consequences of dismissing addiction for such a long time.”

A lack of understanding about addiction, and the “very limited number” of experienced people treating addictions, has contributed to the “huge problem” experts now face in treating addictions, said Dr. Aoun.

“So you want to approach this problem from as many different angles as you can.”

He praised the study for presenting “a framework to ‘medicalize’ the addiction model” for students. This, he said, will help them build empathy and see those with a substance use disorder as no different from other patients with medical conditions.

A curriculum such as the one presented by Dr. Hu and colleagues may spur more medical students into the addiction field, he said. “It may make them more willing to treat patients with addiction using evidence-based medicine rather than dismissing them.”

The study was supported by the Substance Abuse and Mental Health Services Administration.

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

An opioid-centered curriculum for medical students improves awareness of pain management and treatment of opioid use disorder (OUD) and may help mitigate the current opioid crisis in the United States, new research suggests.

“Our study showed that implementing training for medical students about opioid use disorder and its treatment improves knowledge and understanding of clinical principles and may better prepare students to treat patients with this disorder,” study investigator Kimberly Hu, MD, psychiatry resident, Ohio State University, Columbus, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.

The U.S. opioid epidemic claims thousands of lives every year, and there’s evidence it’s getting worse, said Dr. Hu. U.S. data from December 2020 to December 2021 show opioid-related deaths increased by almost 15%.

In 2019, about 70% of the nearly 71,000 drug overdose deaths in the United States involved opioids and now it exceeds 100,000 per year, said Dr. Hu. She noted 80% of heroin users report their addiction started with prescription opioids, data that she described as “pretty staggering.”

Although treatments such as buprenorphine are available for OUD, “insufficient access to medications for opioid use disorder remains a significant barrier for patients,” said Dr. Hu.

“Training the next generation of physicians across all specialties is one way that we can work to improve access to care and improve the health and well-being of our patients.”

The study, which is ongoing, included 405 3rd-year medical students at Ohio State. Researchers provided these students with in-person or virtual (during the pandemic) training in buprenorphine prescribing and in-person clinical experience.

Dr. Hu and her colleagues tested the students before and after the intervention and estimated improvement in knowledge (score 0-23) and approach to clinical management principles (1-5).

The investigators found a statistically significant increase in overall knowledge (from a mean total score of 18.34 to 19.32; P < .001). There was also a statistically significant increase in self-reported understanding of clinical management principles related to screening for and treating OUDs (from a mean of 3.12 to a mean of 4.02; P < .001).

An additional evaluation survey was completed by 162 students at the end of the program. About 83% of these students said they knew how to manage acute pain, 62% felt they knew how to manage chronic pain, and 77% agreed they knew how to screen a patient for OUD.

Dr. Hu noted 3rd-year medical students are a little over halfway through medical school, after which they will go into residency in various specialties. Providing them with this knowledge early on allows them to incorporate it as they continue their training, she said.

“If they are able to screen their patients in any specialty they eventually choose to go into, then they can help link these patients to resources early and make sure there aren’t patients who are slipping through the cracks.”
 

Worthwhile, important research

Howard Liu, MD, chair of the department of psychiatry at the University of Nebraska Medical Center, Omaha, and incoming chair of the APA’s Council on Communications, applauded the study.

The proposed curriculum, he said, instills confidence in students and teaches important lessons they can apply no matter what field they choose.

Dr. Liu, who moderated a press briefing highlighting the study, noted every state is affected differently by the opioid epidemic, but the shortage of appropriate treatments for OUD is nationwide.

Commenting on the study, addiction specialist Elie G. Aoun, MD, of the division of law, medicine, and psychiatry at Columbia University, New York, said this research is “very worthwhile and important.”

He noted that attitudes about addiction need to change. When he taught medical students about substance use disorders, he was struck by some of their negative beliefs about addiction. For example, considering addicts as “junkies” who are “taking resources away” from what they perceive as more deserving patients.

Addiction has been ignored in medicine for too long, added Dr. Aoun. He noted the requirement for addiction training for psychiatry residents is 2 months while they spend 4 months learning internal medicine. “That makes no sense,” he said.

“And now with the opioid epidemic, we’re faced with the consequences of dismissing addiction for such a long time.”

A lack of understanding about addiction, and the “very limited number” of experienced people treating addictions, has contributed to the “huge problem” experts now face in treating addictions, said Dr. Aoun.

“So you want to approach this problem from as many different angles as you can.”

He praised the study for presenting “a framework to ‘medicalize’ the addiction model” for students. This, he said, will help them build empathy and see those with a substance use disorder as no different from other patients with medical conditions.

A curriculum such as the one presented by Dr. Hu and colleagues may spur more medical students into the addiction field, he said. “It may make them more willing to treat patients with addiction using evidence-based medicine rather than dismissing them.”

The study was supported by the Substance Abuse and Mental Health Services Administration.

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