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Ruxolitinib cream for atopic dermatitis found to be effective, safe up to 52 weeks
results from a long-term analysis of clinical trial data showed.
“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.
Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).
According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.
In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.
A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
Longterm data
During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.
Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.
The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.
In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.
“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”
Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.
results from a long-term analysis of clinical trial data showed.
“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.
Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).
According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.
In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.
A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
Longterm data
During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.
Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.
The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.
In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.
“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”
Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.
results from a long-term analysis of clinical trial data showed.
“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.
Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).
According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.
In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.
A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
Longterm data
During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.
Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.
The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.
In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.
“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”
Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.
FROM REVOLUTIONIZING AD 2021
FDA fast-tracks lecanemab for Alzheimer’s disease
Lecanemab (formerly BAN2401) is a humanized monoclonal antibody that selectively binds to large, soluble aggregated Abeta protofibrils. The antibody was developed following the discovery of a mutation in amyloid precursor protein that leads to a form of Alzheimer’s disease that is marked by particularly high levels of Abeta protofibrils.
“As such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease,” Eisai and Biogen said in a joint news release.
The breakthrough therapy designation for lecanemab is based on results of a randomized, double-blind, phase 2b proof-of-concept study published April 17 in Alzheimer’s Research & Therapy.
The study enrolled 856 patients with mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s disease with confirmed presence of amyloid pathology.
At the highest doses, treatment with lecanemab led to a reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints.
Phase 3 testing underway
In March, Eisai and Biogen completed enrollment in a phase 3 study designed to confirm the safety and efficacy of lecanemab in patients with symptomatic early Alzheimer’s disease.
The CLARITY AD study includes 1,795 patients with early Alzheimer’s disease, and initial results are expected by the end of September 2022. The core study will compare lecanemab against placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months. The study will also evaluate the long-term safety and tolerability of lecanemab in the extension phase and whether the long-term effects of lecanemab, as measured by the CDR-SB at the end of the core study, are maintained over time.
Additionally, the phase 3 AHEAD 3-45 clinical study is currently exploring lecanemab in adults with preclinical Alzheimer’s disease (clinically normal but with intermediate or elevated brain amyloid).
On June 7, the FDA – amid significant controversy – approved aducanumab (Aduhelm), the first anti-amyloid agent for the treatment Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug. Three members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee subsequently resigned in protest following the agency’s approval of aducanumab.
In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.
A version of this article first appeared on Medscape.com.
Lecanemab (formerly BAN2401) is a humanized monoclonal antibody that selectively binds to large, soluble aggregated Abeta protofibrils. The antibody was developed following the discovery of a mutation in amyloid precursor protein that leads to a form of Alzheimer’s disease that is marked by particularly high levels of Abeta protofibrils.
“As such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease,” Eisai and Biogen said in a joint news release.
The breakthrough therapy designation for lecanemab is based on results of a randomized, double-blind, phase 2b proof-of-concept study published April 17 in Alzheimer’s Research & Therapy.
The study enrolled 856 patients with mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s disease with confirmed presence of amyloid pathology.
At the highest doses, treatment with lecanemab led to a reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints.
Phase 3 testing underway
In March, Eisai and Biogen completed enrollment in a phase 3 study designed to confirm the safety and efficacy of lecanemab in patients with symptomatic early Alzheimer’s disease.
The CLARITY AD study includes 1,795 patients with early Alzheimer’s disease, and initial results are expected by the end of September 2022. The core study will compare lecanemab against placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months. The study will also evaluate the long-term safety and tolerability of lecanemab in the extension phase and whether the long-term effects of lecanemab, as measured by the CDR-SB at the end of the core study, are maintained over time.
Additionally, the phase 3 AHEAD 3-45 clinical study is currently exploring lecanemab in adults with preclinical Alzheimer’s disease (clinically normal but with intermediate or elevated brain amyloid).
On June 7, the FDA – amid significant controversy – approved aducanumab (Aduhelm), the first anti-amyloid agent for the treatment Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug. Three members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee subsequently resigned in protest following the agency’s approval of aducanumab.
In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.
A version of this article first appeared on Medscape.com.
Lecanemab (formerly BAN2401) is a humanized monoclonal antibody that selectively binds to large, soluble aggregated Abeta protofibrils. The antibody was developed following the discovery of a mutation in amyloid precursor protein that leads to a form of Alzheimer’s disease that is marked by particularly high levels of Abeta protofibrils.
“As such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease,” Eisai and Biogen said in a joint news release.
The breakthrough therapy designation for lecanemab is based on results of a randomized, double-blind, phase 2b proof-of-concept study published April 17 in Alzheimer’s Research & Therapy.
The study enrolled 856 patients with mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s disease with confirmed presence of amyloid pathology.
At the highest doses, treatment with lecanemab led to a reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints.
Phase 3 testing underway
In March, Eisai and Biogen completed enrollment in a phase 3 study designed to confirm the safety and efficacy of lecanemab in patients with symptomatic early Alzheimer’s disease.
The CLARITY AD study includes 1,795 patients with early Alzheimer’s disease, and initial results are expected by the end of September 2022. The core study will compare lecanemab against placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months. The study will also evaluate the long-term safety and tolerability of lecanemab in the extension phase and whether the long-term effects of lecanemab, as measured by the CDR-SB at the end of the core study, are maintained over time.
Additionally, the phase 3 AHEAD 3-45 clinical study is currently exploring lecanemab in adults with preclinical Alzheimer’s disease (clinically normal but with intermediate or elevated brain amyloid).
On June 7, the FDA – amid significant controversy – approved aducanumab (Aduhelm), the first anti-amyloid agent for the treatment Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug. Three members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee subsequently resigned in protest following the agency’s approval of aducanumab.
In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.
A version of this article first appeared on Medscape.com.
Profound brain changes found in patients who died of COVID-19
The most comprehensive molecular study to date of brain tissue from people who died of COVID-19 provides clear evidence that SARS-CoV-2 causes profound molecular changes in the brain, despite no molecular trace of the virus in brain tissue.
“The signature the virus leaves in the brain speaks of strong inflammation and disrupted brain circuits and resembles signatures the field has observed in Alzheimer’s or other neurodegenerative diseases,” senior author Tony Wyss-Coray, PhD, professor of neurology and neurological sciences, Stanford (Calif.) University, told this news organization.
The study was published online June 21 in Nature.
Signs of distress
“We know that up to a third of SARS-CoV-2-infected people show brain symptoms including brain fog, memory problems, and fatigue, and a growing number of people have such symptoms long after they [have] seemingly recovered from virus infection,” said Dr. Wyss-Coray.
“However, we have very little understanding of how the virus causes these symptoms and what its effects are on the brain at a molecular level,” he added.
Using single-cell RNA sequencing, the researchers profiled the transcriptomes of 65,309 nuclei isolated from frontal cortex and choroid plexus samples from eight patients who died of COVID-19 and 14 controls who died of other causes.
There was no molecular evidence of SARS-CoV-2 in brain tissue samples from the patients who died of COVID-19.
Yet, “we were very surprised to learn that no matter which type of cell we studied (different types of nerve cells, immune cells, or different support cells in the brain) there were prominent changes” compared with brain tissue samples from controls who died of other causes, said Dr. Wyss-Coray.
The changes in the COVID-19 brains showed signatures of inflammation, abnormal nerve cell communication, and chronic neurodegeneration.
“Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression,” the researchers report.
“Viral infection appears to trigger inflammatory responses throughout the body that may cause inflammatory signaling across the blood–brain barrier, which in turn could ‘trip off’ neuroinflammation in the brain,” Dr. Wyss-Coray said.
The findings may help explain the brain fog, fatigue, and other neurological and psychiatric symptoms of long COVID.
“While we studied only brains from people who died of COVID-19, we believe it is likely that similar, but hopefully weaker, signs of inflammation and chronic neurodegeneration will be found in COVID-19 survivors, especially those with chronic brain symptoms,” Dr. Wyss-Coray said.
This research was funded by the Nomis Foundation, the National Institutes of Health, Nan Fung Life Sciences, the Wu Tsai Neurosciences Institute and the Stanford Alzheimer’s Disease Research Center. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The most comprehensive molecular study to date of brain tissue from people who died of COVID-19 provides clear evidence that SARS-CoV-2 causes profound molecular changes in the brain, despite no molecular trace of the virus in brain tissue.
“The signature the virus leaves in the brain speaks of strong inflammation and disrupted brain circuits and resembles signatures the field has observed in Alzheimer’s or other neurodegenerative diseases,” senior author Tony Wyss-Coray, PhD, professor of neurology and neurological sciences, Stanford (Calif.) University, told this news organization.
The study was published online June 21 in Nature.
Signs of distress
“We know that up to a third of SARS-CoV-2-infected people show brain symptoms including brain fog, memory problems, and fatigue, and a growing number of people have such symptoms long after they [have] seemingly recovered from virus infection,” said Dr. Wyss-Coray.
“However, we have very little understanding of how the virus causes these symptoms and what its effects are on the brain at a molecular level,” he added.
Using single-cell RNA sequencing, the researchers profiled the transcriptomes of 65,309 nuclei isolated from frontal cortex and choroid plexus samples from eight patients who died of COVID-19 and 14 controls who died of other causes.
There was no molecular evidence of SARS-CoV-2 in brain tissue samples from the patients who died of COVID-19.
Yet, “we were very surprised to learn that no matter which type of cell we studied (different types of nerve cells, immune cells, or different support cells in the brain) there were prominent changes” compared with brain tissue samples from controls who died of other causes, said Dr. Wyss-Coray.
The changes in the COVID-19 brains showed signatures of inflammation, abnormal nerve cell communication, and chronic neurodegeneration.
“Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression,” the researchers report.
“Viral infection appears to trigger inflammatory responses throughout the body that may cause inflammatory signaling across the blood–brain barrier, which in turn could ‘trip off’ neuroinflammation in the brain,” Dr. Wyss-Coray said.
The findings may help explain the brain fog, fatigue, and other neurological and psychiatric symptoms of long COVID.
“While we studied only brains from people who died of COVID-19, we believe it is likely that similar, but hopefully weaker, signs of inflammation and chronic neurodegeneration will be found in COVID-19 survivors, especially those with chronic brain symptoms,” Dr. Wyss-Coray said.
This research was funded by the Nomis Foundation, the National Institutes of Health, Nan Fung Life Sciences, the Wu Tsai Neurosciences Institute and the Stanford Alzheimer’s Disease Research Center. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The most comprehensive molecular study to date of brain tissue from people who died of COVID-19 provides clear evidence that SARS-CoV-2 causes profound molecular changes in the brain, despite no molecular trace of the virus in brain tissue.
“The signature the virus leaves in the brain speaks of strong inflammation and disrupted brain circuits and resembles signatures the field has observed in Alzheimer’s or other neurodegenerative diseases,” senior author Tony Wyss-Coray, PhD, professor of neurology and neurological sciences, Stanford (Calif.) University, told this news organization.
The study was published online June 21 in Nature.
Signs of distress
“We know that up to a third of SARS-CoV-2-infected people show brain symptoms including brain fog, memory problems, and fatigue, and a growing number of people have such symptoms long after they [have] seemingly recovered from virus infection,” said Dr. Wyss-Coray.
“However, we have very little understanding of how the virus causes these symptoms and what its effects are on the brain at a molecular level,” he added.
Using single-cell RNA sequencing, the researchers profiled the transcriptomes of 65,309 nuclei isolated from frontal cortex and choroid plexus samples from eight patients who died of COVID-19 and 14 controls who died of other causes.
There was no molecular evidence of SARS-CoV-2 in brain tissue samples from the patients who died of COVID-19.
Yet, “we were very surprised to learn that no matter which type of cell we studied (different types of nerve cells, immune cells, or different support cells in the brain) there were prominent changes” compared with brain tissue samples from controls who died of other causes, said Dr. Wyss-Coray.
The changes in the COVID-19 brains showed signatures of inflammation, abnormal nerve cell communication, and chronic neurodegeneration.
“Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression,” the researchers report.
“Viral infection appears to trigger inflammatory responses throughout the body that may cause inflammatory signaling across the blood–brain barrier, which in turn could ‘trip off’ neuroinflammation in the brain,” Dr. Wyss-Coray said.
The findings may help explain the brain fog, fatigue, and other neurological and psychiatric symptoms of long COVID.
“While we studied only brains from people who died of COVID-19, we believe it is likely that similar, but hopefully weaker, signs of inflammation and chronic neurodegeneration will be found in COVID-19 survivors, especially those with chronic brain symptoms,” Dr. Wyss-Coray said.
This research was funded by the Nomis Foundation, the National Institutes of Health, Nan Fung Life Sciences, the Wu Tsai Neurosciences Institute and the Stanford Alzheimer’s Disease Research Center. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Dose-dependent effect of ‘internet addiction’ and sleep problems
More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.
Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.
Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.
These sleep problems require attention and correction, Dr. Tereshchenko added.
The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
New phenomenon
IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.
He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.
There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.
However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.
Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.
The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.
The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.
This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).
IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
Siberian students’ sleep
The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.
Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.
In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.
A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”
The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.
Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.
For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.
After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
Sleep disturbance
Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.
Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.
“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.
Decreased total nighttime sleep was more common in older adolescents.
On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.
Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.
Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.
“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.
Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
No escape?
Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”
Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.
Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.
Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.
“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.
Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.
Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.
A version of this article first appeared on Medscape.com.
More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.
Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.
Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.
These sleep problems require attention and correction, Dr. Tereshchenko added.
The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
New phenomenon
IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.
He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.
There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.
However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.
Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.
The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.
The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.
This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).
IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
Siberian students’ sleep
The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.
Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.
In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.
A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”
The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.
Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.
For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.
After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
Sleep disturbance
Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.
Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.
“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.
Decreased total nighttime sleep was more common in older adolescents.
On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.
Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.
Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.
“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.
Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
No escape?
Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”
Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.
Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.
Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.
“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.
Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.
Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.
A version of this article first appeared on Medscape.com.
More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.
Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.
Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.
These sleep problems require attention and correction, Dr. Tereshchenko added.
The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
New phenomenon
IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.
He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.
There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.
However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.
Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.
The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.
The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.
This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).
IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
Siberian students’ sleep
The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.
Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.
In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.
A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”
The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.
Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.
For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.
After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
Sleep disturbance
Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.
Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.
“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.
Decreased total nighttime sleep was more common in older adolescents.
On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.
Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.
Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.
“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.
Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
No escape?
Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”
Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.
Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.
Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.
“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.
Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.
Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.
A version of this article first appeared on Medscape.com.
Guidance provided for telepsychiatry in tardive dyskinesia
Expert panel reviewed best practices in 2020 while pandemic limited in-person visits
Tardive dyskinesia (TD) can be reasonably managed through telemedicine, but it should be employed as part of a hybrid strategy that ideally includes an office visit at the time of diagnosis and yearly intervals thereafter, according to an expert who spoke at a meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In psychiatry in general and in TD specifically, telepsychiatry is useful, but “is not a one-size-fits-all approach,” according to Rif S. El-Mallakh, MD, director of the mood disorder research program at the University of Louisville (Ky.).
Telepsychiatry was already growing as a strategy to expand psychiatric services to communities with limited resources in mental health when the COVID-19 pandemic arrived. Dependence on this type of patient care then exploded out of necessity but in advance of how it might best be applied in specific circumstances.
Best practices panel convened in 2020
The project to develop best practices in TD began in July 2020, when the pandemic was still limiting normal clinician-patient interactions. It was expected from the beginning that recommendations would be applicable to postpandemic circumstances.
There is no reason to expect the forces driving the growth of telepsychiatry, which include convenience of patients and efficiency for clinicians, to dissipate once the pandemic resolves, Dr. El-Mallakh said at the virtual meeting, sponsored by MedscapeLive.
, which consisted of six neurologists, three psychiatrists, and three psychiatric nurse practitioners. The goal was to gather information about the current practice of TD diagnosis and treatment in real-world settings.
With the information on current practices providing a baseline, a virtual roundtable was then convened to develop best-practices recommendations. The deliberations were performed on the basis of expert opinion. There were no statistical methods applied to data collected from the qualitative interviews.
Four key points in recommendations
The panel agreed on four key points: an in-person visit is preferred for initial evaluation and diagnosis; when applied for the evaluation of TD, telepsychiatry should include video; virtual visits cannot completely replace in-person visits; and patients with TD should be evaluated in person at least once per year.
In addition, the panelists recommended specific steps aimed at maximizing the quality of the virtual visit, including confirming that patients have appropriate equipment for video and audio communication. It is also important to recognize that patients or caregivers may require instruction on how to set up the equipment.
Prior to a telemedicine visit, it is appropriate to provide patients with a checklist that includes instructions on adequate lighting and audio. In addition, patient expectations about the goals and processes in the video should be explained.
“Instructional videos prior to the visit might be helpful,” Dr. El-Mallakh said.
Immediately prior to each visit, visual and audio quality should be verified. This allows technical issues, if any, to be resolved.
For the evaluation of TD, the ability to adequately observe body movements is crucial but can pose a challenge in telepsychiatry. To capture hyperkinetic movements and functional impairments with adequate clarity, it might be necessary to engage caregivers to hold the camera or otherwise help the clinician gain an adequate view. Clinicians should consider the limitations of telepsychiatry.
In addition to the challenges of a differential diagnosis for TD that should include such entities as parkinsonism and other drug-induced movement disorders, Dr. El-Mallakh cautioned, “comorbidities add another layer of complexity to TD diagnosis.”
Some in-office visits recommended
It is this complexity that led to the recommendation for an in-person evaluation for new-onset TD, although the expert panel did not characterize an initial in-office visit as mandatory.
Once a diagnosis of TD is established, telepsychiatry can be an efficient strategy for education and for confirming that treatments remain effective. However, Dr. El-Mallakh pointed out that patients can and often do have more than one drug-induced movement disorder at the time of diagnosis or develop additional clinical issues over time.
According to the expert panel, telepsychiatry should not be considered an adequate strategy to manage TD by itself, but “it can be an important component” of care of these patients if used judiciously.
“We have all come to recognize the benefits of telepsychiatry and some of the limitations,” said Jonathan M. Meyer, MD, clinical professor of psychiatry, University of California, San Diego. An author or coauthor of several articles on TD, including a recent study of patient awareness of TD symptoms while on vesicular monoamine transporter 2 inhibitors, Dr. Meyer identified technical problems as among the limitations.
“For movement disorders in particular, low bandwidth, poor video quality and lighting, and inadequate visualization of the trunk and limbs all present issues in diagnosing TD, scoring its severity, and differentiating it from other movement disorders,” he said.
“Nonetheless, I agree with the panel conclusions that in many instances, a video visit can be used to diagnose TD, assess severity, and monitor changes in symptoms over time,” he added, but he did express caution.
“For cases where the diagnosis is in doubt or where comorbid disorders require physical assessment, an in-person examination should be performed before embarking on any TD treatment strategy,” Dr. Meyer said.
MedscapeLive and this news organization are owned by the same parent company. Dr. El-Mallakh has ties with Allergan, Janssen, Lundbeck, Otsuka, Takeda, Teva, and Neurocrine Biosciences, which provided funding for this expert panel and summary. Dr. Meyer has ties with Acadia, Alkermes, Allergan, Merck, Neurocrine, Otsuka, Sunovion, and Teva.
Expert panel reviewed best practices in 2020 while pandemic limited in-person visits
Expert panel reviewed best practices in 2020 while pandemic limited in-person visits
Tardive dyskinesia (TD) can be reasonably managed through telemedicine, but it should be employed as part of a hybrid strategy that ideally includes an office visit at the time of diagnosis and yearly intervals thereafter, according to an expert who spoke at a meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In psychiatry in general and in TD specifically, telepsychiatry is useful, but “is not a one-size-fits-all approach,” according to Rif S. El-Mallakh, MD, director of the mood disorder research program at the University of Louisville (Ky.).
Telepsychiatry was already growing as a strategy to expand psychiatric services to communities with limited resources in mental health when the COVID-19 pandemic arrived. Dependence on this type of patient care then exploded out of necessity but in advance of how it might best be applied in specific circumstances.
Best practices panel convened in 2020
The project to develop best practices in TD began in July 2020, when the pandemic was still limiting normal clinician-patient interactions. It was expected from the beginning that recommendations would be applicable to postpandemic circumstances.
There is no reason to expect the forces driving the growth of telepsychiatry, which include convenience of patients and efficiency for clinicians, to dissipate once the pandemic resolves, Dr. El-Mallakh said at the virtual meeting, sponsored by MedscapeLive.
, which consisted of six neurologists, three psychiatrists, and three psychiatric nurse practitioners. The goal was to gather information about the current practice of TD diagnosis and treatment in real-world settings.
With the information on current practices providing a baseline, a virtual roundtable was then convened to develop best-practices recommendations. The deliberations were performed on the basis of expert opinion. There were no statistical methods applied to data collected from the qualitative interviews.
Four key points in recommendations
The panel agreed on four key points: an in-person visit is preferred for initial evaluation and diagnosis; when applied for the evaluation of TD, telepsychiatry should include video; virtual visits cannot completely replace in-person visits; and patients with TD should be evaluated in person at least once per year.
In addition, the panelists recommended specific steps aimed at maximizing the quality of the virtual visit, including confirming that patients have appropriate equipment for video and audio communication. It is also important to recognize that patients or caregivers may require instruction on how to set up the equipment.
Prior to a telemedicine visit, it is appropriate to provide patients with a checklist that includes instructions on adequate lighting and audio. In addition, patient expectations about the goals and processes in the video should be explained.
“Instructional videos prior to the visit might be helpful,” Dr. El-Mallakh said.
Immediately prior to each visit, visual and audio quality should be verified. This allows technical issues, if any, to be resolved.
For the evaluation of TD, the ability to adequately observe body movements is crucial but can pose a challenge in telepsychiatry. To capture hyperkinetic movements and functional impairments with adequate clarity, it might be necessary to engage caregivers to hold the camera or otherwise help the clinician gain an adequate view. Clinicians should consider the limitations of telepsychiatry.
In addition to the challenges of a differential diagnosis for TD that should include such entities as parkinsonism and other drug-induced movement disorders, Dr. El-Mallakh cautioned, “comorbidities add another layer of complexity to TD diagnosis.”
Some in-office visits recommended
It is this complexity that led to the recommendation for an in-person evaluation for new-onset TD, although the expert panel did not characterize an initial in-office visit as mandatory.
Once a diagnosis of TD is established, telepsychiatry can be an efficient strategy for education and for confirming that treatments remain effective. However, Dr. El-Mallakh pointed out that patients can and often do have more than one drug-induced movement disorder at the time of diagnosis or develop additional clinical issues over time.
According to the expert panel, telepsychiatry should not be considered an adequate strategy to manage TD by itself, but “it can be an important component” of care of these patients if used judiciously.
“We have all come to recognize the benefits of telepsychiatry and some of the limitations,” said Jonathan M. Meyer, MD, clinical professor of psychiatry, University of California, San Diego. An author or coauthor of several articles on TD, including a recent study of patient awareness of TD symptoms while on vesicular monoamine transporter 2 inhibitors, Dr. Meyer identified technical problems as among the limitations.
“For movement disorders in particular, low bandwidth, poor video quality and lighting, and inadequate visualization of the trunk and limbs all present issues in diagnosing TD, scoring its severity, and differentiating it from other movement disorders,” he said.
“Nonetheless, I agree with the panel conclusions that in many instances, a video visit can be used to diagnose TD, assess severity, and monitor changes in symptoms over time,” he added, but he did express caution.
“For cases where the diagnosis is in doubt or where comorbid disorders require physical assessment, an in-person examination should be performed before embarking on any TD treatment strategy,” Dr. Meyer said.
MedscapeLive and this news organization are owned by the same parent company. Dr. El-Mallakh has ties with Allergan, Janssen, Lundbeck, Otsuka, Takeda, Teva, and Neurocrine Biosciences, which provided funding for this expert panel and summary. Dr. Meyer has ties with Acadia, Alkermes, Allergan, Merck, Neurocrine, Otsuka, Sunovion, and Teva.
Tardive dyskinesia (TD) can be reasonably managed through telemedicine, but it should be employed as part of a hybrid strategy that ideally includes an office visit at the time of diagnosis and yearly intervals thereafter, according to an expert who spoke at a meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In psychiatry in general and in TD specifically, telepsychiatry is useful, but “is not a one-size-fits-all approach,” according to Rif S. El-Mallakh, MD, director of the mood disorder research program at the University of Louisville (Ky.).
Telepsychiatry was already growing as a strategy to expand psychiatric services to communities with limited resources in mental health when the COVID-19 pandemic arrived. Dependence on this type of patient care then exploded out of necessity but in advance of how it might best be applied in specific circumstances.
Best practices panel convened in 2020
The project to develop best practices in TD began in July 2020, when the pandemic was still limiting normal clinician-patient interactions. It was expected from the beginning that recommendations would be applicable to postpandemic circumstances.
There is no reason to expect the forces driving the growth of telepsychiatry, which include convenience of patients and efficiency for clinicians, to dissipate once the pandemic resolves, Dr. El-Mallakh said at the virtual meeting, sponsored by MedscapeLive.
, which consisted of six neurologists, three psychiatrists, and three psychiatric nurse practitioners. The goal was to gather information about the current practice of TD diagnosis and treatment in real-world settings.
With the information on current practices providing a baseline, a virtual roundtable was then convened to develop best-practices recommendations. The deliberations were performed on the basis of expert opinion. There were no statistical methods applied to data collected from the qualitative interviews.
Four key points in recommendations
The panel agreed on four key points: an in-person visit is preferred for initial evaluation and diagnosis; when applied for the evaluation of TD, telepsychiatry should include video; virtual visits cannot completely replace in-person visits; and patients with TD should be evaluated in person at least once per year.
In addition, the panelists recommended specific steps aimed at maximizing the quality of the virtual visit, including confirming that patients have appropriate equipment for video and audio communication. It is also important to recognize that patients or caregivers may require instruction on how to set up the equipment.
Prior to a telemedicine visit, it is appropriate to provide patients with a checklist that includes instructions on adequate lighting and audio. In addition, patient expectations about the goals and processes in the video should be explained.
“Instructional videos prior to the visit might be helpful,” Dr. El-Mallakh said.
Immediately prior to each visit, visual and audio quality should be verified. This allows technical issues, if any, to be resolved.
For the evaluation of TD, the ability to adequately observe body movements is crucial but can pose a challenge in telepsychiatry. To capture hyperkinetic movements and functional impairments with adequate clarity, it might be necessary to engage caregivers to hold the camera or otherwise help the clinician gain an adequate view. Clinicians should consider the limitations of telepsychiatry.
In addition to the challenges of a differential diagnosis for TD that should include such entities as parkinsonism and other drug-induced movement disorders, Dr. El-Mallakh cautioned, “comorbidities add another layer of complexity to TD diagnosis.”
Some in-office visits recommended
It is this complexity that led to the recommendation for an in-person evaluation for new-onset TD, although the expert panel did not characterize an initial in-office visit as mandatory.
Once a diagnosis of TD is established, telepsychiatry can be an efficient strategy for education and for confirming that treatments remain effective. However, Dr. El-Mallakh pointed out that patients can and often do have more than one drug-induced movement disorder at the time of diagnosis or develop additional clinical issues over time.
According to the expert panel, telepsychiatry should not be considered an adequate strategy to manage TD by itself, but “it can be an important component” of care of these patients if used judiciously.
“We have all come to recognize the benefits of telepsychiatry and some of the limitations,” said Jonathan M. Meyer, MD, clinical professor of psychiatry, University of California, San Diego. An author or coauthor of several articles on TD, including a recent study of patient awareness of TD symptoms while on vesicular monoamine transporter 2 inhibitors, Dr. Meyer identified technical problems as among the limitations.
“For movement disorders in particular, low bandwidth, poor video quality and lighting, and inadequate visualization of the trunk and limbs all present issues in diagnosing TD, scoring its severity, and differentiating it from other movement disorders,” he said.
“Nonetheless, I agree with the panel conclusions that in many instances, a video visit can be used to diagnose TD, assess severity, and monitor changes in symptoms over time,” he added, but he did express caution.
“For cases where the diagnosis is in doubt or where comorbid disorders require physical assessment, an in-person examination should be performed before embarking on any TD treatment strategy,” Dr. Meyer said.
MedscapeLive and this news organization are owned by the same parent company. Dr. El-Mallakh has ties with Allergan, Janssen, Lundbeck, Otsuka, Takeda, Teva, and Neurocrine Biosciences, which provided funding for this expert panel and summary. Dr. Meyer has ties with Acadia, Alkermes, Allergan, Merck, Neurocrine, Otsuka, Sunovion, and Teva.
FROM CP/AACP PSYCHIATRY UPDATE
MD jailed for road rage, career spirals downhill
It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.
“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”
The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.
“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”
The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.
Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.
“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
The physician ends up in jail
After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said.
When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.
“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”
Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance.
In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.
“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
‘I like to drive fast’
Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.
The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.
“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ”
Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.
“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”
After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.
“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”
After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.
Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.
“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”
The Florida State Attorney’s Office did not return messages seeking comment about the case.
Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
New evidence lowers charges
Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.
Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.
“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”
The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.
“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”
With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing.
“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”
Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.
“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”
About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case.
“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
A short-lived celebration
Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him.
But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.
“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”
Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.
A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.
According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.
The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.
Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.
In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.
“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”
Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
A new career path
Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.
“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”
Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.
Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.
Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.
“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”
Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.
“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”
A version of this article first appeared on Medscape.com.
It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.
“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”
The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.
“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”
The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.
Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.
“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
The physician ends up in jail
After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said.
When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.
“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”
Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance.
In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.
“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
‘I like to drive fast’
Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.
The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.
“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ”
Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.
“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”
After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.
“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”
After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.
Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.
“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”
The Florida State Attorney’s Office did not return messages seeking comment about the case.
Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
New evidence lowers charges
Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.
Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.
“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”
The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.
“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”
With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing.
“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”
Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.
“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”
About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case.
“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
A short-lived celebration
Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him.
But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.
“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”
Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.
A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.
According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.
The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.
Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.
In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.
“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”
Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
A new career path
Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.
“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”
Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.
Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.
Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.
“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”
Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.
“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”
A version of this article first appeared on Medscape.com.
It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.
“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”
The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.
“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”
The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.
Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.
“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
The physician ends up in jail
After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said.
When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.
“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”
Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance.
In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.
“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
‘I like to drive fast’
Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.
The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.
“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ”
Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.
“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”
After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.
“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”
After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.
Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.
“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”
The Florida State Attorney’s Office did not return messages seeking comment about the case.
Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
New evidence lowers charges
Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.
Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.
“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”
The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.
“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”
With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing.
“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”
Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.
“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”
About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case.
“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
A short-lived celebration
Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him.
But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.
“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”
Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.
A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.
According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.
The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.
Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.
In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.
“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”
Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
A new career path
Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.
“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”
Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.
Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.
Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.
“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”
Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.
“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”
A version of this article first appeared on Medscape.com.
ADHD: Presentation and Diagnosis
ADHD – The Basics
FDA leader explains rationale leading to controversial Alzheimer’s drug approval
, including the release of several internal documents.
In a letter sent to members of the FDA’s Center for Drug Evaluation Research (CDER), CDER Director Patrizia Cavazzoni, MD, noted that in view of the “fierce public debate” that erupted immediately following the drug’s approval, she felt compelled to explain how the agency came to its decision.
Also publicly released today on the FDA’s updated aducanumab landing page was “the first set of review memos,” for the drug.
“We’re releasing these documents with the intent of informing public discourse – providing interested parties with the opportunity to explore the data that helped shape our decision to grant accelerated approval,” Dr. Cavazzoni wrote. “The rest of the approval package will be released over the next several days,” she added.
Immediate backlash
The FDA’s June 7 approval of aducanumab was met with instant backlash. In November 2020, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee voted nearly unanimously to not vote in favor of approval because of a lack of evidence proving its efficacy.
Since the drug was approved, three of the advisory committee’s members resigned in protest. In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.
In its letter, the group noted that the FDA’s decision “showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”
Even the Alzheimer’s Association, which was a staunch supporter of the drug throughout its development process and applauded its approval, expressed outrage over its more than $56,000-a-year cost to patients and called the price “simply unacceptable” in a statement.
In the June 23 letter, the CDER director noted, “this was one of the most complex applications in recent history” and admitted that deliberations were lengthy and difficult.
“It’s also not surprising, in fact it was to be expected, that there would be different viewpoints about the data, including dissenting opinions about the approval decision,” Dr. Cavazzoni wrote.
However, this “is what scientific debate is all about, and while difficult at times, it should be celebrated,” she added. “Please know that every opinion was heard, and the approval is a direct reflection of this open and robust scientific and regulatory debate.”
Accelerated approval pathway
Documents newly posted to the FDA’s aducanumab landing page include CDER’s Office of Neurology’s Summary Review Memorandum, which includes details on the basis for the approval; the Concurrence Memorandum from the director of CDER’s Office of New Drugs; and the Concurrence Memorandum from Dr. Cavazzoni.
“The remaining scientific review documents in the Aduhelm action package are not yet available but will be made available to the public as soon as the internal process of review and redaction is complete,” the FDA noted on its site.
In the document FDA’s Decision to Approve New Treatment for Alzheimer’s Disease, Dr. Cavazzoni noted that the “highly complex” data included in the submission package for the drug “left residual uncertainties regarding clinical benefit.”
However, after listening to the patient community and reviewing all the data, the FDA chose to use the Accelerated Approval pathway, deciding that the potential benefit to patients outweighed the drug’s risks.
Of two phase 3 trials, only one met its primary endpoint. However, in all trials, including earlier studies, “Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion,” Dr. Cavazzoni wrote.
“It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” she added.
Dr. Cavazzoni noted that although the Advisory Committee did not agree that clinical benefit from one trial meeting its primary endpoint was enough for approval, “the option of Accelerated Approval was not discussed” at that time.
This type of approval “is based on a surrogate or intermediate clinical endpoint, in this case reduction of amyloid plaque in the brain” and requires post-approval studies to verify clinical benefit.
Dr. Cavazzoni added that the drug could still be removed from the market if its confirmatory trial does not verify this type of benefit.
A version of this article first appeared on Medscape.com.
, including the release of several internal documents.
In a letter sent to members of the FDA’s Center for Drug Evaluation Research (CDER), CDER Director Patrizia Cavazzoni, MD, noted that in view of the “fierce public debate” that erupted immediately following the drug’s approval, she felt compelled to explain how the agency came to its decision.
Also publicly released today on the FDA’s updated aducanumab landing page was “the first set of review memos,” for the drug.
“We’re releasing these documents with the intent of informing public discourse – providing interested parties with the opportunity to explore the data that helped shape our decision to grant accelerated approval,” Dr. Cavazzoni wrote. “The rest of the approval package will be released over the next several days,” she added.
Immediate backlash
The FDA’s June 7 approval of aducanumab was met with instant backlash. In November 2020, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee voted nearly unanimously to not vote in favor of approval because of a lack of evidence proving its efficacy.
Since the drug was approved, three of the advisory committee’s members resigned in protest. In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.
In its letter, the group noted that the FDA’s decision “showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”
Even the Alzheimer’s Association, which was a staunch supporter of the drug throughout its development process and applauded its approval, expressed outrage over its more than $56,000-a-year cost to patients and called the price “simply unacceptable” in a statement.
In the June 23 letter, the CDER director noted, “this was one of the most complex applications in recent history” and admitted that deliberations were lengthy and difficult.
“It’s also not surprising, in fact it was to be expected, that there would be different viewpoints about the data, including dissenting opinions about the approval decision,” Dr. Cavazzoni wrote.
However, this “is what scientific debate is all about, and while difficult at times, it should be celebrated,” she added. “Please know that every opinion was heard, and the approval is a direct reflection of this open and robust scientific and regulatory debate.”
Accelerated approval pathway
Documents newly posted to the FDA’s aducanumab landing page include CDER’s Office of Neurology’s Summary Review Memorandum, which includes details on the basis for the approval; the Concurrence Memorandum from the director of CDER’s Office of New Drugs; and the Concurrence Memorandum from Dr. Cavazzoni.
“The remaining scientific review documents in the Aduhelm action package are not yet available but will be made available to the public as soon as the internal process of review and redaction is complete,” the FDA noted on its site.
In the document FDA’s Decision to Approve New Treatment for Alzheimer’s Disease, Dr. Cavazzoni noted that the “highly complex” data included in the submission package for the drug “left residual uncertainties regarding clinical benefit.”
However, after listening to the patient community and reviewing all the data, the FDA chose to use the Accelerated Approval pathway, deciding that the potential benefit to patients outweighed the drug’s risks.
Of two phase 3 trials, only one met its primary endpoint. However, in all trials, including earlier studies, “Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion,” Dr. Cavazzoni wrote.
“It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” she added.
Dr. Cavazzoni noted that although the Advisory Committee did not agree that clinical benefit from one trial meeting its primary endpoint was enough for approval, “the option of Accelerated Approval was not discussed” at that time.
This type of approval “is based on a surrogate or intermediate clinical endpoint, in this case reduction of amyloid plaque in the brain” and requires post-approval studies to verify clinical benefit.
Dr. Cavazzoni added that the drug could still be removed from the market if its confirmatory trial does not verify this type of benefit.
A version of this article first appeared on Medscape.com.
, including the release of several internal documents.
In a letter sent to members of the FDA’s Center for Drug Evaluation Research (CDER), CDER Director Patrizia Cavazzoni, MD, noted that in view of the “fierce public debate” that erupted immediately following the drug’s approval, she felt compelled to explain how the agency came to its decision.
Also publicly released today on the FDA’s updated aducanumab landing page was “the first set of review memos,” for the drug.
“We’re releasing these documents with the intent of informing public discourse – providing interested parties with the opportunity to explore the data that helped shape our decision to grant accelerated approval,” Dr. Cavazzoni wrote. “The rest of the approval package will be released over the next several days,” she added.
Immediate backlash
The FDA’s June 7 approval of aducanumab was met with instant backlash. In November 2020, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee voted nearly unanimously to not vote in favor of approval because of a lack of evidence proving its efficacy.
Since the drug was approved, three of the advisory committee’s members resigned in protest. In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.
In its letter, the group noted that the FDA’s decision “showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”
Even the Alzheimer’s Association, which was a staunch supporter of the drug throughout its development process and applauded its approval, expressed outrage over its more than $56,000-a-year cost to patients and called the price “simply unacceptable” in a statement.
In the June 23 letter, the CDER director noted, “this was one of the most complex applications in recent history” and admitted that deliberations were lengthy and difficult.
“It’s also not surprising, in fact it was to be expected, that there would be different viewpoints about the data, including dissenting opinions about the approval decision,” Dr. Cavazzoni wrote.
However, this “is what scientific debate is all about, and while difficult at times, it should be celebrated,” she added. “Please know that every opinion was heard, and the approval is a direct reflection of this open and robust scientific and regulatory debate.”
Accelerated approval pathway
Documents newly posted to the FDA’s aducanumab landing page include CDER’s Office of Neurology’s Summary Review Memorandum, which includes details on the basis for the approval; the Concurrence Memorandum from the director of CDER’s Office of New Drugs; and the Concurrence Memorandum from Dr. Cavazzoni.
“The remaining scientific review documents in the Aduhelm action package are not yet available but will be made available to the public as soon as the internal process of review and redaction is complete,” the FDA noted on its site.
In the document FDA’s Decision to Approve New Treatment for Alzheimer’s Disease, Dr. Cavazzoni noted that the “highly complex” data included in the submission package for the drug “left residual uncertainties regarding clinical benefit.”
However, after listening to the patient community and reviewing all the data, the FDA chose to use the Accelerated Approval pathway, deciding that the potential benefit to patients outweighed the drug’s risks.
Of two phase 3 trials, only one met its primary endpoint. However, in all trials, including earlier studies, “Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion,” Dr. Cavazzoni wrote.
“It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” she added.
Dr. Cavazzoni noted that although the Advisory Committee did not agree that clinical benefit from one trial meeting its primary endpoint was enough for approval, “the option of Accelerated Approval was not discussed” at that time.
This type of approval “is based on a surrogate or intermediate clinical endpoint, in this case reduction of amyloid plaque in the brain” and requires post-approval studies to verify clinical benefit.
Dr. Cavazzoni added that the drug could still be removed from the market if its confirmatory trial does not verify this type of benefit.
A version of this article first appeared on Medscape.com.
Noted ability of Mozart’s music to reduce seizures explained?
– and now researchers believe they know why.
Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.
Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.
The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
Clinically controversial?
Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.
Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.
A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.
American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.
However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”
The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.
Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.
Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
Surprising finding
Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.
Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.
“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.
He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.
Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.
The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.
In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).
“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.
Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
A new theory
Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.
“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.
The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.
Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.
While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.
The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.
“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
‘Inspiring research’
Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.
She questioned whether factors other than gender may predict response to music.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
– and now researchers believe they know why.
Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.
Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.
The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
Clinically controversial?
Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.
Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.
A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.
American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.
However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”
The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.
Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.
Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
Surprising finding
Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.
Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.
“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.
He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.
Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.
The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.
In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).
“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.
Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
A new theory
Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.
“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.
The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.
Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.
While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.
The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.
“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
‘Inspiring research’
Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.
She questioned whether factors other than gender may predict response to music.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
– and now researchers believe they know why.
Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.
Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.
The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
Clinically controversial?
Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.
Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.
A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.
American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.
However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”
The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.
Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.
Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
Surprising finding
Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.
Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.
“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.
He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.
Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.
The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.
In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).
“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.
Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
A new theory
Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.
“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.
The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.
Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.
While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.
The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.
“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
‘Inspiring research’
Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.
She questioned whether factors other than gender may predict response to music.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EAN 2021