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TBI Significantly Increases Mortality Rate Among Veterans With Epilepsy
, according to recent research published in Epilepsia.
In a retrospective cohort study, Ali Roghani, PhD, of the division of epidemiology at the University of Utah School of Medicine in Salt Lake City, and colleagues evaluated 938,890 veterans between 2000 and 2019 in the Defense Health Agency and the Veterans Health Administration who served in the US military after the September 11 attacks. Overall, 27,436 veterans met criteria for a diagnosis of epilepsy, 264,890 had received a diagnosis for a traumatic brain injury (TBI), and the remaining patients had neither epilepsy nor TBI.
Among the veterans with no epilepsy, 248,714 veterans had a TBI diagnosis, while in the group of patients with epilepsy, 10,358 veterans experienced a TBI before their epilepsy diagnosis, 1598 were diagnosed with a TBI within 6 months of epilepsy, and 4310 veterans had a TBI 6 months after an epilepsy diagnosis. The researchers assessed all-cause mortality in each group, calculating cumulative mortality rates compared with the group of veterans who had no TBI and no epilepsy diagnosis.
Dr. Roghani and colleagues found a significantly higher mortality rate among veterans who developed epilepsy compared with a control group with neither epilepsy nor TBI (6.26% vs. 1.12%; P < .01), with a majority of veterans in the group who died being White (67.4%) men (89.9%). Compared with veterans who were deceased, nondeceased veterans were significantly more likely to have a history of being deployed (70.7% vs. 64.8%; P < .001), were less likely to be in the army (52.2% vs. 55.0%; P < .001), and were more likely to reach the rank of officer or warrant officer (8.1% vs. 7.6%; P = .014).
There were also significant differences in clinical characteristics between nondeceased and deceased veterans, including a higher rate of substance abuse disorder, smoking history, cardiovascular disease, stroke, transient ischemic attack, cancer, liver disease, kidney disease, or other injury as well as overdose, suicidal ideation, and homelessness. “Most clinical conditions were significantly different between deceased and nondeceased in part due to the large cohort size,” the researchers said.
After performing Cox regression analyses, the researchers found a higher mortality risk in veterans with epilepsy and/or TBIs among those who developed a TBI within 6 months of an epilepsy diagnosis (hazard ratio [HR], 5.02; 95% CI, 4.21-5.99), had a TBI prior to epilepsy (HR, 4.25; 95% CI, 3.89-4.58), had epilepsy alone (HR, 4.00; 95% CI, 3.67-4.36), had a TBI more than 6 months after an epilepsy diagnosis (HR, 2.49; 95% CI, 2.17-2.85), and those who had epilepsy alone (HR, 1.30; 95% CI, 1.25-1.36) compared with veterans who had neither epilepsy nor a TBI.
“The temporal relationship with TBI that occurred within 6 months after epilepsy diagnosis may suggest an increased vulnerability to accidents, severe injuries, or TBI resulting from seizures, potentially elevating mortality risk,” Dr. Roghani and colleagues wrote.
The researchers said the results “raise concerns” about the subgroup of patients who are diagnosed with epilepsy close to experiencing a TBI.
“Our results provide information regarding the temporal relationship between epilepsy and TBI regarding mortality in a cohort of post-9/11 veterans, which highlights the need for enhanced primary prevention, such as more access to health care among people with epilepsy and TBI,” they said. “Given the rising incidence of TBI in both the military and civilian populations, these findings suggest close monitoring might be crucial to develop effective prevention strategies for long-term complications, particularly [post-traumatic epilepsy].”
Reevaluating the Treatment of Epilepsy
Juliann Paolicchi, MD, a neurologist and member of the epilepsy team at Northwell Health in New York, who was not involved with the study, said in an interview that TBIs have been studied more closely since the beginning of conflicts in the Middle East, particularly in Iran and Afghanistan, where “newer artillery causes more diffuse traumatic injury to the brain and the body than the effects of more typical weaponry.”
The study by Roghani and colleagues, she said, “is groundbreaking in that it looks at the connection and timing of these two disruptive forces, epilepsy and TBI, on the brain,” she said. “The study reveals that timing is everything: The combination of two disrupting circuitry effects in proximity can have a deadly effect. The summation is greater than either alone in veterans, and has significant effects on the brain’s ability to sustain the functions that keep us alive.”
The 6 months following either a diagnosis of epilepsy or TBI is “crucial,” Dr. Paolicchi noted. “Military and private citizens should be closely monitored during this period, and the results suggest they should refrain from activities that could predispose to further brain injury.”
In addition, current standards for treatment of epilepsy may need to be reevaluated, she said. “Patients are not always treated with a seizure medication after a first seizure, but perhaps, especially in patients at higher risk for brain injury such as the military and athletes, that policy warrants further examination.”
The findings by Roghani and colleagues may also extend to other groups, such as evaluating athletes after a concussion, patients after they are in a motor vehicle accident, and infants with traumatic brain injury, Dr. Paolicchi said. “The results suggest a reexamining of the proximity [of TBI] and epilepsy in these and other areas,” she noted.
The authors reported personal and institutional relationships in the form of research support and other financial compensation from AbbVie, Biohaven, CURE, Department of Defense, Department of Veterans Affairs (VA), Eisai, Engage, National Institutes of Health, Sanofi, SCS Consulting, Sunovion, and UCB. This study was supported by funding from the Department of Defense, VA Health Systems, and the VA HSR&D Informatics, Decision Enhancement, and Analytic Sciences Center of Innovation. Dr. Paolicchi reports no relevant conflicts of interest.
, according to recent research published in Epilepsia.
In a retrospective cohort study, Ali Roghani, PhD, of the division of epidemiology at the University of Utah School of Medicine in Salt Lake City, and colleagues evaluated 938,890 veterans between 2000 and 2019 in the Defense Health Agency and the Veterans Health Administration who served in the US military after the September 11 attacks. Overall, 27,436 veterans met criteria for a diagnosis of epilepsy, 264,890 had received a diagnosis for a traumatic brain injury (TBI), and the remaining patients had neither epilepsy nor TBI.
Among the veterans with no epilepsy, 248,714 veterans had a TBI diagnosis, while in the group of patients with epilepsy, 10,358 veterans experienced a TBI before their epilepsy diagnosis, 1598 were diagnosed with a TBI within 6 months of epilepsy, and 4310 veterans had a TBI 6 months after an epilepsy diagnosis. The researchers assessed all-cause mortality in each group, calculating cumulative mortality rates compared with the group of veterans who had no TBI and no epilepsy diagnosis.
Dr. Roghani and colleagues found a significantly higher mortality rate among veterans who developed epilepsy compared with a control group with neither epilepsy nor TBI (6.26% vs. 1.12%; P < .01), with a majority of veterans in the group who died being White (67.4%) men (89.9%). Compared with veterans who were deceased, nondeceased veterans were significantly more likely to have a history of being deployed (70.7% vs. 64.8%; P < .001), were less likely to be in the army (52.2% vs. 55.0%; P < .001), and were more likely to reach the rank of officer or warrant officer (8.1% vs. 7.6%; P = .014).
There were also significant differences in clinical characteristics between nondeceased and deceased veterans, including a higher rate of substance abuse disorder, smoking history, cardiovascular disease, stroke, transient ischemic attack, cancer, liver disease, kidney disease, or other injury as well as overdose, suicidal ideation, and homelessness. “Most clinical conditions were significantly different between deceased and nondeceased in part due to the large cohort size,” the researchers said.
After performing Cox regression analyses, the researchers found a higher mortality risk in veterans with epilepsy and/or TBIs among those who developed a TBI within 6 months of an epilepsy diagnosis (hazard ratio [HR], 5.02; 95% CI, 4.21-5.99), had a TBI prior to epilepsy (HR, 4.25; 95% CI, 3.89-4.58), had epilepsy alone (HR, 4.00; 95% CI, 3.67-4.36), had a TBI more than 6 months after an epilepsy diagnosis (HR, 2.49; 95% CI, 2.17-2.85), and those who had epilepsy alone (HR, 1.30; 95% CI, 1.25-1.36) compared with veterans who had neither epilepsy nor a TBI.
“The temporal relationship with TBI that occurred within 6 months after epilepsy diagnosis may suggest an increased vulnerability to accidents, severe injuries, or TBI resulting from seizures, potentially elevating mortality risk,” Dr. Roghani and colleagues wrote.
The researchers said the results “raise concerns” about the subgroup of patients who are diagnosed with epilepsy close to experiencing a TBI.
“Our results provide information regarding the temporal relationship between epilepsy and TBI regarding mortality in a cohort of post-9/11 veterans, which highlights the need for enhanced primary prevention, such as more access to health care among people with epilepsy and TBI,” they said. “Given the rising incidence of TBI in both the military and civilian populations, these findings suggest close monitoring might be crucial to develop effective prevention strategies for long-term complications, particularly [post-traumatic epilepsy].”
Reevaluating the Treatment of Epilepsy
Juliann Paolicchi, MD, a neurologist and member of the epilepsy team at Northwell Health in New York, who was not involved with the study, said in an interview that TBIs have been studied more closely since the beginning of conflicts in the Middle East, particularly in Iran and Afghanistan, where “newer artillery causes more diffuse traumatic injury to the brain and the body than the effects of more typical weaponry.”
The study by Roghani and colleagues, she said, “is groundbreaking in that it looks at the connection and timing of these two disruptive forces, epilepsy and TBI, on the brain,” she said. “The study reveals that timing is everything: The combination of two disrupting circuitry effects in proximity can have a deadly effect. The summation is greater than either alone in veterans, and has significant effects on the brain’s ability to sustain the functions that keep us alive.”
The 6 months following either a diagnosis of epilepsy or TBI is “crucial,” Dr. Paolicchi noted. “Military and private citizens should be closely monitored during this period, and the results suggest they should refrain from activities that could predispose to further brain injury.”
In addition, current standards for treatment of epilepsy may need to be reevaluated, she said. “Patients are not always treated with a seizure medication after a first seizure, but perhaps, especially in patients at higher risk for brain injury such as the military and athletes, that policy warrants further examination.”
The findings by Roghani and colleagues may also extend to other groups, such as evaluating athletes after a concussion, patients after they are in a motor vehicle accident, and infants with traumatic brain injury, Dr. Paolicchi said. “The results suggest a reexamining of the proximity [of TBI] and epilepsy in these and other areas,” she noted.
The authors reported personal and institutional relationships in the form of research support and other financial compensation from AbbVie, Biohaven, CURE, Department of Defense, Department of Veterans Affairs (VA), Eisai, Engage, National Institutes of Health, Sanofi, SCS Consulting, Sunovion, and UCB. This study was supported by funding from the Department of Defense, VA Health Systems, and the VA HSR&D Informatics, Decision Enhancement, and Analytic Sciences Center of Innovation. Dr. Paolicchi reports no relevant conflicts of interest.
, according to recent research published in Epilepsia.
In a retrospective cohort study, Ali Roghani, PhD, of the division of epidemiology at the University of Utah School of Medicine in Salt Lake City, and colleagues evaluated 938,890 veterans between 2000 and 2019 in the Defense Health Agency and the Veterans Health Administration who served in the US military after the September 11 attacks. Overall, 27,436 veterans met criteria for a diagnosis of epilepsy, 264,890 had received a diagnosis for a traumatic brain injury (TBI), and the remaining patients had neither epilepsy nor TBI.
Among the veterans with no epilepsy, 248,714 veterans had a TBI diagnosis, while in the group of patients with epilepsy, 10,358 veterans experienced a TBI before their epilepsy diagnosis, 1598 were diagnosed with a TBI within 6 months of epilepsy, and 4310 veterans had a TBI 6 months after an epilepsy diagnosis. The researchers assessed all-cause mortality in each group, calculating cumulative mortality rates compared with the group of veterans who had no TBI and no epilepsy diagnosis.
Dr. Roghani and colleagues found a significantly higher mortality rate among veterans who developed epilepsy compared with a control group with neither epilepsy nor TBI (6.26% vs. 1.12%; P < .01), with a majority of veterans in the group who died being White (67.4%) men (89.9%). Compared with veterans who were deceased, nondeceased veterans were significantly more likely to have a history of being deployed (70.7% vs. 64.8%; P < .001), were less likely to be in the army (52.2% vs. 55.0%; P < .001), and were more likely to reach the rank of officer or warrant officer (8.1% vs. 7.6%; P = .014).
There were also significant differences in clinical characteristics between nondeceased and deceased veterans, including a higher rate of substance abuse disorder, smoking history, cardiovascular disease, stroke, transient ischemic attack, cancer, liver disease, kidney disease, or other injury as well as overdose, suicidal ideation, and homelessness. “Most clinical conditions were significantly different between deceased and nondeceased in part due to the large cohort size,” the researchers said.
After performing Cox regression analyses, the researchers found a higher mortality risk in veterans with epilepsy and/or TBIs among those who developed a TBI within 6 months of an epilepsy diagnosis (hazard ratio [HR], 5.02; 95% CI, 4.21-5.99), had a TBI prior to epilepsy (HR, 4.25; 95% CI, 3.89-4.58), had epilepsy alone (HR, 4.00; 95% CI, 3.67-4.36), had a TBI more than 6 months after an epilepsy diagnosis (HR, 2.49; 95% CI, 2.17-2.85), and those who had epilepsy alone (HR, 1.30; 95% CI, 1.25-1.36) compared with veterans who had neither epilepsy nor a TBI.
“The temporal relationship with TBI that occurred within 6 months after epilepsy diagnosis may suggest an increased vulnerability to accidents, severe injuries, or TBI resulting from seizures, potentially elevating mortality risk,” Dr. Roghani and colleagues wrote.
The researchers said the results “raise concerns” about the subgroup of patients who are diagnosed with epilepsy close to experiencing a TBI.
“Our results provide information regarding the temporal relationship between epilepsy and TBI regarding mortality in a cohort of post-9/11 veterans, which highlights the need for enhanced primary prevention, such as more access to health care among people with epilepsy and TBI,” they said. “Given the rising incidence of TBI in both the military and civilian populations, these findings suggest close monitoring might be crucial to develop effective prevention strategies for long-term complications, particularly [post-traumatic epilepsy].”
Reevaluating the Treatment of Epilepsy
Juliann Paolicchi, MD, a neurologist and member of the epilepsy team at Northwell Health in New York, who was not involved with the study, said in an interview that TBIs have been studied more closely since the beginning of conflicts in the Middle East, particularly in Iran and Afghanistan, where “newer artillery causes more diffuse traumatic injury to the brain and the body than the effects of more typical weaponry.”
The study by Roghani and colleagues, she said, “is groundbreaking in that it looks at the connection and timing of these two disruptive forces, epilepsy and TBI, on the brain,” she said. “The study reveals that timing is everything: The combination of two disrupting circuitry effects in proximity can have a deadly effect. The summation is greater than either alone in veterans, and has significant effects on the brain’s ability to sustain the functions that keep us alive.”
The 6 months following either a diagnosis of epilepsy or TBI is “crucial,” Dr. Paolicchi noted. “Military and private citizens should be closely monitored during this period, and the results suggest they should refrain from activities that could predispose to further brain injury.”
In addition, current standards for treatment of epilepsy may need to be reevaluated, she said. “Patients are not always treated with a seizure medication after a first seizure, but perhaps, especially in patients at higher risk for brain injury such as the military and athletes, that policy warrants further examination.”
The findings by Roghani and colleagues may also extend to other groups, such as evaluating athletes after a concussion, patients after they are in a motor vehicle accident, and infants with traumatic brain injury, Dr. Paolicchi said. “The results suggest a reexamining of the proximity [of TBI] and epilepsy in these and other areas,” she noted.
The authors reported personal and institutional relationships in the form of research support and other financial compensation from AbbVie, Biohaven, CURE, Department of Defense, Department of Veterans Affairs (VA), Eisai, Engage, National Institutes of Health, Sanofi, SCS Consulting, Sunovion, and UCB. This study was supported by funding from the Department of Defense, VA Health Systems, and the VA HSR&D Informatics, Decision Enhancement, and Analytic Sciences Center of Innovation. Dr. Paolicchi reports no relevant conflicts of interest.
FROM EPILEPSIA
Scientist Aims to Unravel Long COVID’s Neurologic Impacts
Neurologic symptoms of long COVID are vast, common, hard to treat, disabling, and can mimic dozens of other syndromes, with some symptoms as serious as those seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS).
Now, recent evidence has suggested long COVID is primarily an autonomic nervous system disorder.
Their lives may never be the same.
Lindsay S. McAlpine, MD, a specialist in the neurologic sequelae of COVID-19 at the Yale School of Medicine and director of the Yale NeuroCOVID Clinic, New Haven, Connecticut, treats patients who struggle with neurologic symptoms even after disease recovery.
“Some people have the brain fog and the shortness of breath; some have the palpitations and the headaches ... it’s kind of a mix and match,” she said.
Dr. McAlpine’s research has been slowly building up into what could bring about a significant breakthrough in treating some of the most misunderstood and difficult-to-treat symptoms of long COVID.
The Effect of Vascular Inflammation on Long COVID
The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”
Using advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, McAlpine hopes to unearth and better understand the pathophysiology behind neurologic issues post-COVID.
Dr. McAlpine said, “What we’re seeing is that there’s a unique signature of vascular inflammation in long COVID that is distinct from acute COVID. And it has to do with endothelial apathy and platelet dysfunction.”
She’s also looking into whether microvascular dysfunction could increase one’s risk for small vessel disease. Her research is quantitatively building an overall pathophysiology piece by piece.
“We’re quantifying cognitive dysfunction and using objective testing ... a very rigorous 3-hour protocol to really identify the patterns of weakness until we find deficits in memory working and declarative memory, deficits in executive functioning, and others. Those are the three pieces that I’m trying to piece together: The MRI, the blood work, and the cognitive testing,” she said.
Ultimately, Dr. McAlpine believes long COVID will eventually be classified as a peripheral autonomic disorder. The damage being wrought to the whole body also damages the brain’s vasculature, and Dr. McAlpine’s MRI techniques probe at this connection.
“Some of my MRI techniques are dependent on the very subtle changes in blood flow to different regions in response to demand. Brain fog has been a key symptom of POTS and ME/CFS. And it’s now a key symptom of long COVID ... what I’m looking at in some of my studies is how and in which parts of the brain are affected by this,” she said.
Dr. McAlpine’s interest in COVID’s effect on our nervous system goes back all the way to the first wave of patients with COVID, where she noticed an unusually high incidence of ischemic stroke.
“We recognized that COVID really has a huge impact on the vessels ... there’s quite a bit of vascular inflammation. In terms of neurology, we were seeing quite a bit of ischemic stroke, which is unusual,” she said.
Patients don’t normally present with stroke while infected with a virus. Seeking answers, she conducted a stroke study in patients with acute COVID and found profound endotheliopathy — damage to key cells in the lining of blood vessels — leading to a cascade of dysfunction and clotting.
A Constellation of Neuropsychiatric Symptoms
In early June, Dr. McAlpine gave a presentation of her research at the Demystifying Long COVID North American Conference 2024 in Boston. She’s been hard at work in extrapolating the causes of neuropsychiatric long COVID, a tangled web of symptoms seen in patients with long COVID that range from cognitive dysfunction to headaches, neuropathy, mental health, and the aforementioned dysautonomia.
Amid the sea of neurologic long COVID symptoms, she said “symptoms that are mixing and matching are very similar. So, I wanted to specifically look at a symptom that I could definitely isolate to the brain, and that is brain fog and cognitive dysfunction and impairment.”
In September 2021, the journal Translational Psychiatry published a study titled “Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.”
Going back all the way to the first cases of COVID in March 2020, the initial symptoms most patients complained of during an acute viral infection were around the respiratory system. Yet delirium, confusion, and neurocognitive disorders were also reported, puzzling experts and inciting a well-founded fear among many.
Even worse, after recovery, these neuropsychiatric symptoms persisted. The study found that coronavirus was able to invade the central nervous system through blood vessels and neuronal retrograde pathways, leading to brain injury and dysfunction of the cardiorespiratory center in the brainstem.
The study concluded by reporting that neuroimaging and neurochemical evidence indicated neuroimmune dysfunction and brain injury in severe patients with COVID-19. Suggested treatments included immunosuppressive therapies, vaccines to target the coronavirus’ spike protein, and pharmacological agents to improve endothelial integrity.
But there was still much that was unknown, and the study’s authors stressed the need for multidisciplinary research going forward.
How Immune Dysfunction Plays a Role
Similarly, Dr. McAlpine and her research team are still trying to sift their way through this opaque web to see why long COVID can cause autoimmune flare-ups.
In a study published in April, Dr. McAlpine and others found that small fiber neuropathy (SFN) after COVID is autoimmune-mediated and a dysfunction of the immune system.
Notably, they found that SFN could be a key pathologic finding in long COVID. SFN before the pandemic had been linked to ME/CFS and POTS, and the basic hypothesis revolved around an inflammatory immune response during a viral illness that may lead to immune dysregulation (dysimmunity) and damage to small fiber nerves.
But much still remains to be answered.
“We’ve seen quite a bit of that, but we still haven’t figured it out,” Dr. McAlpine said. “My big question is, how is this autonomic dysfunction related to the immune dysfunction, and how is that related to the vascular inflammation? There’s quite a bit of overlap in individuals with autoimmune disease and those who go on to develop this long COVID,” she added.
Still, a large portion of patients with long COVID don’t show autoimmune dysfunction, and those patients lack common biomarkers for an autoimmune condition.
“When we look at the spinal fluid in those individuals [with multiple sclerosis or a neuroinfectious disease], there’s inflammation going on ... the white blood cell count is elevated, the protein is elevated, the antibodies, the bands are elevated. I’ve been seeing long COVID patients now for 4 years, and their presentation is so distinctly different compared to my individuals that I see my patients with MS, or a neuroinfectious disease,” she said.
The mechanisms behind how all of this is interlaced remain unclear, and there may not be a one-size-fits-all treatment or definite pathogenesis for everyone.
“It’s that intersection of the immune system and the vessel wall ... Next is to figure out what do we treat, what are the targets, all of that, but there’s so many different presentations, and everybody has kind of a unique case,” she said.
How Physician Can Treat Common Symptoms Now
Though a cure for symptoms still eludes the scientific community, recent evidence has suggested that a combination of N-acetyl cysteine (NAC) and guanfacine has been successful in easing neurologic symptoms.
In November 2023, Arman Fesharaki-Zadeh, MD, PhD, a Yale Medicine behavioral neurologist and neuropsychiatrist, published a small study in Neuroimmunology Reports with his colleague, Yale neuroscientist Amy Arnsten, PhD. The two researchers showed how among 12 patients given 600 mg NAC daily, along with 1 mg guanfacine (increased to 2 mg after a month if well-tolerated), eight demonstrated improved cognitive abilities.
In patients who stayed on guanfacine + NAC, improved working memory, concentration, and executive functions were seen.
Also, they resumed their normal work schedule. Interruption and inability to work has been a significant factor in the lower quality-of-life long COVID patients experience.
Placebo-controlled trials will be needed going forward, but their small study has established safety and could open up a larger study in the future. For the moment, NAC can be gotten over the counter, and patients could get a prescription off-label from their doctor.
Dr. McAlpine has seen this combination work well for her own patients at Yale’s NeuroCOVID clinic.
Additionally, lifestyle practices such as quitting tobacco, increased exercise, exercising the mind, lowering alcohol intake, and even vitamin D supplementation (1000-2000 IU daily) could prove beneficial in tamping down persistent brain fog.
Vitamin D supports brain and nerve function through its reduction of brain aging biomarkers, regulating genes important for brain function, activating and deactivating enzymes important for neurotransmitter synthesis, and supporting neuronal growth and survival.
A version of this article first appeared on Medscape.com.
Neurologic symptoms of long COVID are vast, common, hard to treat, disabling, and can mimic dozens of other syndromes, with some symptoms as serious as those seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS).
Now, recent evidence has suggested long COVID is primarily an autonomic nervous system disorder.
Their lives may never be the same.
Lindsay S. McAlpine, MD, a specialist in the neurologic sequelae of COVID-19 at the Yale School of Medicine and director of the Yale NeuroCOVID Clinic, New Haven, Connecticut, treats patients who struggle with neurologic symptoms even after disease recovery.
“Some people have the brain fog and the shortness of breath; some have the palpitations and the headaches ... it’s kind of a mix and match,” she said.
Dr. McAlpine’s research has been slowly building up into what could bring about a significant breakthrough in treating some of the most misunderstood and difficult-to-treat symptoms of long COVID.
The Effect of Vascular Inflammation on Long COVID
The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”
Using advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, McAlpine hopes to unearth and better understand the pathophysiology behind neurologic issues post-COVID.
Dr. McAlpine said, “What we’re seeing is that there’s a unique signature of vascular inflammation in long COVID that is distinct from acute COVID. And it has to do with endothelial apathy and platelet dysfunction.”
She’s also looking into whether microvascular dysfunction could increase one’s risk for small vessel disease. Her research is quantitatively building an overall pathophysiology piece by piece.
“We’re quantifying cognitive dysfunction and using objective testing ... a very rigorous 3-hour protocol to really identify the patterns of weakness until we find deficits in memory working and declarative memory, deficits in executive functioning, and others. Those are the three pieces that I’m trying to piece together: The MRI, the blood work, and the cognitive testing,” she said.
Ultimately, Dr. McAlpine believes long COVID will eventually be classified as a peripheral autonomic disorder. The damage being wrought to the whole body also damages the brain’s vasculature, and Dr. McAlpine’s MRI techniques probe at this connection.
“Some of my MRI techniques are dependent on the very subtle changes in blood flow to different regions in response to demand. Brain fog has been a key symptom of POTS and ME/CFS. And it’s now a key symptom of long COVID ... what I’m looking at in some of my studies is how and in which parts of the brain are affected by this,” she said.
Dr. McAlpine’s interest in COVID’s effect on our nervous system goes back all the way to the first wave of patients with COVID, where she noticed an unusually high incidence of ischemic stroke.
“We recognized that COVID really has a huge impact on the vessels ... there’s quite a bit of vascular inflammation. In terms of neurology, we were seeing quite a bit of ischemic stroke, which is unusual,” she said.
Patients don’t normally present with stroke while infected with a virus. Seeking answers, she conducted a stroke study in patients with acute COVID and found profound endotheliopathy — damage to key cells in the lining of blood vessels — leading to a cascade of dysfunction and clotting.
A Constellation of Neuropsychiatric Symptoms
In early June, Dr. McAlpine gave a presentation of her research at the Demystifying Long COVID North American Conference 2024 in Boston. She’s been hard at work in extrapolating the causes of neuropsychiatric long COVID, a tangled web of symptoms seen in patients with long COVID that range from cognitive dysfunction to headaches, neuropathy, mental health, and the aforementioned dysautonomia.
Amid the sea of neurologic long COVID symptoms, she said “symptoms that are mixing and matching are very similar. So, I wanted to specifically look at a symptom that I could definitely isolate to the brain, and that is brain fog and cognitive dysfunction and impairment.”
In September 2021, the journal Translational Psychiatry published a study titled “Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.”
Going back all the way to the first cases of COVID in March 2020, the initial symptoms most patients complained of during an acute viral infection were around the respiratory system. Yet delirium, confusion, and neurocognitive disorders were also reported, puzzling experts and inciting a well-founded fear among many.
Even worse, after recovery, these neuropsychiatric symptoms persisted. The study found that coronavirus was able to invade the central nervous system through blood vessels and neuronal retrograde pathways, leading to brain injury and dysfunction of the cardiorespiratory center in the brainstem.
The study concluded by reporting that neuroimaging and neurochemical evidence indicated neuroimmune dysfunction and brain injury in severe patients with COVID-19. Suggested treatments included immunosuppressive therapies, vaccines to target the coronavirus’ spike protein, and pharmacological agents to improve endothelial integrity.
But there was still much that was unknown, and the study’s authors stressed the need for multidisciplinary research going forward.
How Immune Dysfunction Plays a Role
Similarly, Dr. McAlpine and her research team are still trying to sift their way through this opaque web to see why long COVID can cause autoimmune flare-ups.
In a study published in April, Dr. McAlpine and others found that small fiber neuropathy (SFN) after COVID is autoimmune-mediated and a dysfunction of the immune system.
Notably, they found that SFN could be a key pathologic finding in long COVID. SFN before the pandemic had been linked to ME/CFS and POTS, and the basic hypothesis revolved around an inflammatory immune response during a viral illness that may lead to immune dysregulation (dysimmunity) and damage to small fiber nerves.
But much still remains to be answered.
“We’ve seen quite a bit of that, but we still haven’t figured it out,” Dr. McAlpine said. “My big question is, how is this autonomic dysfunction related to the immune dysfunction, and how is that related to the vascular inflammation? There’s quite a bit of overlap in individuals with autoimmune disease and those who go on to develop this long COVID,” she added.
Still, a large portion of patients with long COVID don’t show autoimmune dysfunction, and those patients lack common biomarkers for an autoimmune condition.
“When we look at the spinal fluid in those individuals [with multiple sclerosis or a neuroinfectious disease], there’s inflammation going on ... the white blood cell count is elevated, the protein is elevated, the antibodies, the bands are elevated. I’ve been seeing long COVID patients now for 4 years, and their presentation is so distinctly different compared to my individuals that I see my patients with MS, or a neuroinfectious disease,” she said.
The mechanisms behind how all of this is interlaced remain unclear, and there may not be a one-size-fits-all treatment or definite pathogenesis for everyone.
“It’s that intersection of the immune system and the vessel wall ... Next is to figure out what do we treat, what are the targets, all of that, but there’s so many different presentations, and everybody has kind of a unique case,” she said.
How Physician Can Treat Common Symptoms Now
Though a cure for symptoms still eludes the scientific community, recent evidence has suggested that a combination of N-acetyl cysteine (NAC) and guanfacine has been successful in easing neurologic symptoms.
In November 2023, Arman Fesharaki-Zadeh, MD, PhD, a Yale Medicine behavioral neurologist and neuropsychiatrist, published a small study in Neuroimmunology Reports with his colleague, Yale neuroscientist Amy Arnsten, PhD. The two researchers showed how among 12 patients given 600 mg NAC daily, along with 1 mg guanfacine (increased to 2 mg after a month if well-tolerated), eight demonstrated improved cognitive abilities.
In patients who stayed on guanfacine + NAC, improved working memory, concentration, and executive functions were seen.
Also, they resumed their normal work schedule. Interruption and inability to work has been a significant factor in the lower quality-of-life long COVID patients experience.
Placebo-controlled trials will be needed going forward, but their small study has established safety and could open up a larger study in the future. For the moment, NAC can be gotten over the counter, and patients could get a prescription off-label from their doctor.
Dr. McAlpine has seen this combination work well for her own patients at Yale’s NeuroCOVID clinic.
Additionally, lifestyle practices such as quitting tobacco, increased exercise, exercising the mind, lowering alcohol intake, and even vitamin D supplementation (1000-2000 IU daily) could prove beneficial in tamping down persistent brain fog.
Vitamin D supports brain and nerve function through its reduction of brain aging biomarkers, regulating genes important for brain function, activating and deactivating enzymes important for neurotransmitter synthesis, and supporting neuronal growth and survival.
A version of this article first appeared on Medscape.com.
Neurologic symptoms of long COVID are vast, common, hard to treat, disabling, and can mimic dozens of other syndromes, with some symptoms as serious as those seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS).
Now, recent evidence has suggested long COVID is primarily an autonomic nervous system disorder.
Their lives may never be the same.
Lindsay S. McAlpine, MD, a specialist in the neurologic sequelae of COVID-19 at the Yale School of Medicine and director of the Yale NeuroCOVID Clinic, New Haven, Connecticut, treats patients who struggle with neurologic symptoms even after disease recovery.
“Some people have the brain fog and the shortness of breath; some have the palpitations and the headaches ... it’s kind of a mix and match,” she said.
Dr. McAlpine’s research has been slowly building up into what could bring about a significant breakthrough in treating some of the most misunderstood and difficult-to-treat symptoms of long COVID.
The Effect of Vascular Inflammation on Long COVID
The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”
Using advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, McAlpine hopes to unearth and better understand the pathophysiology behind neurologic issues post-COVID.
Dr. McAlpine said, “What we’re seeing is that there’s a unique signature of vascular inflammation in long COVID that is distinct from acute COVID. And it has to do with endothelial apathy and platelet dysfunction.”
She’s also looking into whether microvascular dysfunction could increase one’s risk for small vessel disease. Her research is quantitatively building an overall pathophysiology piece by piece.
“We’re quantifying cognitive dysfunction and using objective testing ... a very rigorous 3-hour protocol to really identify the patterns of weakness until we find deficits in memory working and declarative memory, deficits in executive functioning, and others. Those are the three pieces that I’m trying to piece together: The MRI, the blood work, and the cognitive testing,” she said.
Ultimately, Dr. McAlpine believes long COVID will eventually be classified as a peripheral autonomic disorder. The damage being wrought to the whole body also damages the brain’s vasculature, and Dr. McAlpine’s MRI techniques probe at this connection.
“Some of my MRI techniques are dependent on the very subtle changes in blood flow to different regions in response to demand. Brain fog has been a key symptom of POTS and ME/CFS. And it’s now a key symptom of long COVID ... what I’m looking at in some of my studies is how and in which parts of the brain are affected by this,” she said.
Dr. McAlpine’s interest in COVID’s effect on our nervous system goes back all the way to the first wave of patients with COVID, where she noticed an unusually high incidence of ischemic stroke.
“We recognized that COVID really has a huge impact on the vessels ... there’s quite a bit of vascular inflammation. In terms of neurology, we were seeing quite a bit of ischemic stroke, which is unusual,” she said.
Patients don’t normally present with stroke while infected with a virus. Seeking answers, she conducted a stroke study in patients with acute COVID and found profound endotheliopathy — damage to key cells in the lining of blood vessels — leading to a cascade of dysfunction and clotting.
A Constellation of Neuropsychiatric Symptoms
In early June, Dr. McAlpine gave a presentation of her research at the Demystifying Long COVID North American Conference 2024 in Boston. She’s been hard at work in extrapolating the causes of neuropsychiatric long COVID, a tangled web of symptoms seen in patients with long COVID that range from cognitive dysfunction to headaches, neuropathy, mental health, and the aforementioned dysautonomia.
Amid the sea of neurologic long COVID symptoms, she said “symptoms that are mixing and matching are very similar. So, I wanted to specifically look at a symptom that I could definitely isolate to the brain, and that is brain fog and cognitive dysfunction and impairment.”
In September 2021, the journal Translational Psychiatry published a study titled “Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.”
Going back all the way to the first cases of COVID in March 2020, the initial symptoms most patients complained of during an acute viral infection were around the respiratory system. Yet delirium, confusion, and neurocognitive disorders were also reported, puzzling experts and inciting a well-founded fear among many.
Even worse, after recovery, these neuropsychiatric symptoms persisted. The study found that coronavirus was able to invade the central nervous system through blood vessels and neuronal retrograde pathways, leading to brain injury and dysfunction of the cardiorespiratory center in the brainstem.
The study concluded by reporting that neuroimaging and neurochemical evidence indicated neuroimmune dysfunction and brain injury in severe patients with COVID-19. Suggested treatments included immunosuppressive therapies, vaccines to target the coronavirus’ spike protein, and pharmacological agents to improve endothelial integrity.
But there was still much that was unknown, and the study’s authors stressed the need for multidisciplinary research going forward.
How Immune Dysfunction Plays a Role
Similarly, Dr. McAlpine and her research team are still trying to sift their way through this opaque web to see why long COVID can cause autoimmune flare-ups.
In a study published in April, Dr. McAlpine and others found that small fiber neuropathy (SFN) after COVID is autoimmune-mediated and a dysfunction of the immune system.
Notably, they found that SFN could be a key pathologic finding in long COVID. SFN before the pandemic had been linked to ME/CFS and POTS, and the basic hypothesis revolved around an inflammatory immune response during a viral illness that may lead to immune dysregulation (dysimmunity) and damage to small fiber nerves.
But much still remains to be answered.
“We’ve seen quite a bit of that, but we still haven’t figured it out,” Dr. McAlpine said. “My big question is, how is this autonomic dysfunction related to the immune dysfunction, and how is that related to the vascular inflammation? There’s quite a bit of overlap in individuals with autoimmune disease and those who go on to develop this long COVID,” she added.
Still, a large portion of patients with long COVID don’t show autoimmune dysfunction, and those patients lack common biomarkers for an autoimmune condition.
“When we look at the spinal fluid in those individuals [with multiple sclerosis or a neuroinfectious disease], there’s inflammation going on ... the white blood cell count is elevated, the protein is elevated, the antibodies, the bands are elevated. I’ve been seeing long COVID patients now for 4 years, and their presentation is so distinctly different compared to my individuals that I see my patients with MS, or a neuroinfectious disease,” she said.
The mechanisms behind how all of this is interlaced remain unclear, and there may not be a one-size-fits-all treatment or definite pathogenesis for everyone.
“It’s that intersection of the immune system and the vessel wall ... Next is to figure out what do we treat, what are the targets, all of that, but there’s so many different presentations, and everybody has kind of a unique case,” she said.
How Physician Can Treat Common Symptoms Now
Though a cure for symptoms still eludes the scientific community, recent evidence has suggested that a combination of N-acetyl cysteine (NAC) and guanfacine has been successful in easing neurologic symptoms.
In November 2023, Arman Fesharaki-Zadeh, MD, PhD, a Yale Medicine behavioral neurologist and neuropsychiatrist, published a small study in Neuroimmunology Reports with his colleague, Yale neuroscientist Amy Arnsten, PhD. The two researchers showed how among 12 patients given 600 mg NAC daily, along with 1 mg guanfacine (increased to 2 mg after a month if well-tolerated), eight demonstrated improved cognitive abilities.
In patients who stayed on guanfacine + NAC, improved working memory, concentration, and executive functions were seen.
Also, they resumed their normal work schedule. Interruption and inability to work has been a significant factor in the lower quality-of-life long COVID patients experience.
Placebo-controlled trials will be needed going forward, but their small study has established safety and could open up a larger study in the future. For the moment, NAC can be gotten over the counter, and patients could get a prescription off-label from their doctor.
Dr. McAlpine has seen this combination work well for her own patients at Yale’s NeuroCOVID clinic.
Additionally, lifestyle practices such as quitting tobacco, increased exercise, exercising the mind, lowering alcohol intake, and even vitamin D supplementation (1000-2000 IU daily) could prove beneficial in tamping down persistent brain fog.
Vitamin D supports brain and nerve function through its reduction of brain aging biomarkers, regulating genes important for brain function, activating and deactivating enzymes important for neurotransmitter synthesis, and supporting neuronal growth and survival.
A version of this article first appeared on Medscape.com.
New Parkinson’s Disease Gene Discovered
HELSINKI, FINLAND — , a discovery that experts believe will have important clinical implications in the not-too-distant future.
A variant in PMSF1, a proteasome regulator, was identified in 15 families from 13 countries around the world, with 22 affected individuals.
“These families were ethnically diverse, and in all of them, the variant in PMSF1 correlated with the neurologic phenotype. We know this is very clear cut — the genotype/phenotype correlation — with the patients carrying the missense mutation having ‘mild’ symptoms, while those with the progressive loss-of-function variant had the most severe phenotype,” she noted.
“Our findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor,” study investigator Francesca Magrinelli, MD, PhD, of University College London (UCL) Queen Square Institute of Neurology, UCL, London, told delegates at the 2024 Congress of the European Academy of Neurology.
Managing Patient Expectations
Those “mildly” affected had an early-onset Parkinson’s disease starting between the second and fifth decade of life with pyramidal tract signs, dysphasia, psychiatric comorbidity, and early levodopa-induced dyskinesia.
In those with the intermediate type, Parkinson’s disease symptoms start in childhood and include, among other things, global hypokinesia, developmental delay, cerebellar signs, and in some, associated epilepsy.
In most cases, there was evidence on brain MRI of a hypoplasia of the corpus callosum, Dr. Magrinelli said. In the most severely affected individuals, there was perinatal lethality with neurologic manifestations.
While it may seem that the genetics of Parkinson’s disease is an academic exercise for the most part, it won’t be too much longer before it yields practical information that will inform how patients are treated, said Parkinson’s disease expert Christine Klein, MD, of the Institute of Neurogenetics and Department of Neurology, University of Lübeck, Helsinki, Finland.
The genetics of Parkinson’s disease are complicated, even within a single family. So, it’s very important to assess the pathogenicity of different variants, Dr. Klein noted.
“I am sure that you have all had a Parkinson’s disease [gene] panel back, and it says, ‘variant of uncertain significance.’ This is the worst thing that can happen. The lab does not know what it means. You don’t know what it means, and you don’t know what to tell the patient. So how do you get around this?”
Dr. Klein said that before conducting any genetic testing, clinicians should inform the patient that they may have a genetic variant of uncertain significance. It doesn’t solve the problem, but it does help physicians manage patient expectations.
Clinical Relevance on the Way?
While it may seem that all of the identified variants that predict Parkinson’s disease which, in addition to PSMF1, include the well-established LRRK2 and GBA1, may look the same, this is not true when patient history is taken into account, said Dr. Klein.
For example, age-of-onset of Parkinson’s disease can differ between identified variants, and this has led to “a paradigm change” whereby a purely genetic finding is called a disease.
This first occurred in Huntington’s disease, when researchers gave individuals at high genetic risk of developing the illness, but who currently had no clinical symptoms, the label of “Stage Zero disease.”
This is important to note “because if we get to the stage of having drugs that can slow down, or even prevent, progression to Parkinson’s disease, then it will be key to have patients we know are going to develop it to participate in clinical trials for such agents,” said Dr. Klein.
She cited the example of a family that she recently encountered that had genetic test results that showed variants of unknown significance, so Dr. Klein had the family’s samples sent to a specialized lab in Dundee, Scotland, for further analysis.
“The biochemists found that this variant was indeed pathogenic, and kinase-activating, so this is very helpful and very important because there are now clinical trials in Parkinson’s disease with kinase inhibitors,” she noted.
“If you think there is something else [over and above the finding of uncertain significance] in your Parkinson’s disease panel, and you are not happy with the genetic report, send it somewhere else,” Dr. Klein advised.
“We will see a lot more patients with genetic Parkinson’s disease in the future,” she predicted, while citing two recent preliminary clinical trials that have shown some promise in terms of neuroprotection in patients with early Parkinson’s disease.
“It remains to be seen whether there will be light at the end of the tunnel,” she said, but it may soon be possible to find treatments that delay, or even prevent, Parkinson’s disease onset.
Dr. Magrinelli reported receiving speaker’s honoraria from MJFF Edmond J. Safra Clinical Research Fellowship in Movement Disorders (Class of 2023), MJFF Edmond J. Safra Movement Disorders Research Career Development Award 2023 (Grant ID MJFF-023893), American Parkinson Disease Association (Research Grant 2024), and the David Blank Charitable Foundation. Dr. Klein reported being a medical advisor to Retromer Therapeutics, Takeda, and Centogene and speakers’ honoraria from Desitin and Bial.
A version of this article first appeared on Medscape.com.
HELSINKI, FINLAND — , a discovery that experts believe will have important clinical implications in the not-too-distant future.
A variant in PMSF1, a proteasome regulator, was identified in 15 families from 13 countries around the world, with 22 affected individuals.
“These families were ethnically diverse, and in all of them, the variant in PMSF1 correlated with the neurologic phenotype. We know this is very clear cut — the genotype/phenotype correlation — with the patients carrying the missense mutation having ‘mild’ symptoms, while those with the progressive loss-of-function variant had the most severe phenotype,” she noted.
“Our findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor,” study investigator Francesca Magrinelli, MD, PhD, of University College London (UCL) Queen Square Institute of Neurology, UCL, London, told delegates at the 2024 Congress of the European Academy of Neurology.
Managing Patient Expectations
Those “mildly” affected had an early-onset Parkinson’s disease starting between the second and fifth decade of life with pyramidal tract signs, dysphasia, psychiatric comorbidity, and early levodopa-induced dyskinesia.
In those with the intermediate type, Parkinson’s disease symptoms start in childhood and include, among other things, global hypokinesia, developmental delay, cerebellar signs, and in some, associated epilepsy.
In most cases, there was evidence on brain MRI of a hypoplasia of the corpus callosum, Dr. Magrinelli said. In the most severely affected individuals, there was perinatal lethality with neurologic manifestations.
While it may seem that the genetics of Parkinson’s disease is an academic exercise for the most part, it won’t be too much longer before it yields practical information that will inform how patients are treated, said Parkinson’s disease expert Christine Klein, MD, of the Institute of Neurogenetics and Department of Neurology, University of Lübeck, Helsinki, Finland.
The genetics of Parkinson’s disease are complicated, even within a single family. So, it’s very important to assess the pathogenicity of different variants, Dr. Klein noted.
“I am sure that you have all had a Parkinson’s disease [gene] panel back, and it says, ‘variant of uncertain significance.’ This is the worst thing that can happen. The lab does not know what it means. You don’t know what it means, and you don’t know what to tell the patient. So how do you get around this?”
Dr. Klein said that before conducting any genetic testing, clinicians should inform the patient that they may have a genetic variant of uncertain significance. It doesn’t solve the problem, but it does help physicians manage patient expectations.
Clinical Relevance on the Way?
While it may seem that all of the identified variants that predict Parkinson’s disease which, in addition to PSMF1, include the well-established LRRK2 and GBA1, may look the same, this is not true when patient history is taken into account, said Dr. Klein.
For example, age-of-onset of Parkinson’s disease can differ between identified variants, and this has led to “a paradigm change” whereby a purely genetic finding is called a disease.
This first occurred in Huntington’s disease, when researchers gave individuals at high genetic risk of developing the illness, but who currently had no clinical symptoms, the label of “Stage Zero disease.”
This is important to note “because if we get to the stage of having drugs that can slow down, or even prevent, progression to Parkinson’s disease, then it will be key to have patients we know are going to develop it to participate in clinical trials for such agents,” said Dr. Klein.
She cited the example of a family that she recently encountered that had genetic test results that showed variants of unknown significance, so Dr. Klein had the family’s samples sent to a specialized lab in Dundee, Scotland, for further analysis.
“The biochemists found that this variant was indeed pathogenic, and kinase-activating, so this is very helpful and very important because there are now clinical trials in Parkinson’s disease with kinase inhibitors,” she noted.
“If you think there is something else [over and above the finding of uncertain significance] in your Parkinson’s disease panel, and you are not happy with the genetic report, send it somewhere else,” Dr. Klein advised.
“We will see a lot more patients with genetic Parkinson’s disease in the future,” she predicted, while citing two recent preliminary clinical trials that have shown some promise in terms of neuroprotection in patients with early Parkinson’s disease.
“It remains to be seen whether there will be light at the end of the tunnel,” she said, but it may soon be possible to find treatments that delay, or even prevent, Parkinson’s disease onset.
Dr. Magrinelli reported receiving speaker’s honoraria from MJFF Edmond J. Safra Clinical Research Fellowship in Movement Disorders (Class of 2023), MJFF Edmond J. Safra Movement Disorders Research Career Development Award 2023 (Grant ID MJFF-023893), American Parkinson Disease Association (Research Grant 2024), and the David Blank Charitable Foundation. Dr. Klein reported being a medical advisor to Retromer Therapeutics, Takeda, and Centogene and speakers’ honoraria from Desitin and Bial.
A version of this article first appeared on Medscape.com.
HELSINKI, FINLAND — , a discovery that experts believe will have important clinical implications in the not-too-distant future.
A variant in PMSF1, a proteasome regulator, was identified in 15 families from 13 countries around the world, with 22 affected individuals.
“These families were ethnically diverse, and in all of them, the variant in PMSF1 correlated with the neurologic phenotype. We know this is very clear cut — the genotype/phenotype correlation — with the patients carrying the missense mutation having ‘mild’ symptoms, while those with the progressive loss-of-function variant had the most severe phenotype,” she noted.
“Our findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor,” study investigator Francesca Magrinelli, MD, PhD, of University College London (UCL) Queen Square Institute of Neurology, UCL, London, told delegates at the 2024 Congress of the European Academy of Neurology.
Managing Patient Expectations
Those “mildly” affected had an early-onset Parkinson’s disease starting between the second and fifth decade of life with pyramidal tract signs, dysphasia, psychiatric comorbidity, and early levodopa-induced dyskinesia.
In those with the intermediate type, Parkinson’s disease symptoms start in childhood and include, among other things, global hypokinesia, developmental delay, cerebellar signs, and in some, associated epilepsy.
In most cases, there was evidence on brain MRI of a hypoplasia of the corpus callosum, Dr. Magrinelli said. In the most severely affected individuals, there was perinatal lethality with neurologic manifestations.
While it may seem that the genetics of Parkinson’s disease is an academic exercise for the most part, it won’t be too much longer before it yields practical information that will inform how patients are treated, said Parkinson’s disease expert Christine Klein, MD, of the Institute of Neurogenetics and Department of Neurology, University of Lübeck, Helsinki, Finland.
The genetics of Parkinson’s disease are complicated, even within a single family. So, it’s very important to assess the pathogenicity of different variants, Dr. Klein noted.
“I am sure that you have all had a Parkinson’s disease [gene] panel back, and it says, ‘variant of uncertain significance.’ This is the worst thing that can happen. The lab does not know what it means. You don’t know what it means, and you don’t know what to tell the patient. So how do you get around this?”
Dr. Klein said that before conducting any genetic testing, clinicians should inform the patient that they may have a genetic variant of uncertain significance. It doesn’t solve the problem, but it does help physicians manage patient expectations.
Clinical Relevance on the Way?
While it may seem that all of the identified variants that predict Parkinson’s disease which, in addition to PSMF1, include the well-established LRRK2 and GBA1, may look the same, this is not true when patient history is taken into account, said Dr. Klein.
For example, age-of-onset of Parkinson’s disease can differ between identified variants, and this has led to “a paradigm change” whereby a purely genetic finding is called a disease.
This first occurred in Huntington’s disease, when researchers gave individuals at high genetic risk of developing the illness, but who currently had no clinical symptoms, the label of “Stage Zero disease.”
This is important to note “because if we get to the stage of having drugs that can slow down, or even prevent, progression to Parkinson’s disease, then it will be key to have patients we know are going to develop it to participate in clinical trials for such agents,” said Dr. Klein.
She cited the example of a family that she recently encountered that had genetic test results that showed variants of unknown significance, so Dr. Klein had the family’s samples sent to a specialized lab in Dundee, Scotland, for further analysis.
“The biochemists found that this variant was indeed pathogenic, and kinase-activating, so this is very helpful and very important because there are now clinical trials in Parkinson’s disease with kinase inhibitors,” she noted.
“If you think there is something else [over and above the finding of uncertain significance] in your Parkinson’s disease panel, and you are not happy with the genetic report, send it somewhere else,” Dr. Klein advised.
“We will see a lot more patients with genetic Parkinson’s disease in the future,” she predicted, while citing two recent preliminary clinical trials that have shown some promise in terms of neuroprotection in patients with early Parkinson’s disease.
“It remains to be seen whether there will be light at the end of the tunnel,” she said, but it may soon be possible to find treatments that delay, or even prevent, Parkinson’s disease onset.
Dr. Magrinelli reported receiving speaker’s honoraria from MJFF Edmond J. Safra Clinical Research Fellowship in Movement Disorders (Class of 2023), MJFF Edmond J. Safra Movement Disorders Research Career Development Award 2023 (Grant ID MJFF-023893), American Parkinson Disease Association (Research Grant 2024), and the David Blank Charitable Foundation. Dr. Klein reported being a medical advisor to Retromer Therapeutics, Takeda, and Centogene and speakers’ honoraria from Desitin and Bial.
A version of this article first appeared on Medscape.com.
FROM EAN 2024
Revamping Resident Schedules to Reduce Burnout
It’s the difference between running a marathon and taking a leisurely stroll. That’s how recent pediatrics resident Joey Whelihan, MD, compared an 11-hour inpatient hospital day with an 8-hour outpatient shift where residents see patients in a clinic.
With inpatient training, “you are lucky if you have time to cook dinner, go to bed, and get ready for the next day,” said Dr. Whelihan, who recently started his adolescent medicine fellowship at Children’s Hospital of Philadelphia after 3 years of residency there. Some residents have call every fourth day during inpatient rotations, working 24-28 hours at a time. They come in one morning and go home the next, he told this news organization.
“Outpatient blocks give you more time to catch your breath and feel somewhat refreshed and ready to take care of patients.”
Longer stretches of inpatient rotations are not sustainable, Dr. Whelihan added, and residents are likely to become exhausted. Fatigue is a leading cause of burnout, a mental, physical, and emotional challenge that residency programs and national medical organizations have been struggling to address.
In recent years, there has been a movement to reduce the maximum consecutive duration of resident duty hours in residency programs across the country. Fueled by resident health and patient safety concerns, the movement is a shift from the previous 24- to 36-hour call duty schedules.
Improved Call Systems = Better Residents
The connection between burnout, well-being, and work schedules appears regularly in national program standards. “Residents and faculty members are at risk for burnout and depression,” according to the current Accreditation Council for Graduate Medical Education’s standard residency program requirements.
“Programs, in partnership with their sponsoring institutions, have the same responsibility to address well-being as other aspects of resident competence,” the guidelines state. That charge includes “attention to scheduling, work intensity, and work compression that impacts resident well-being.”
In Medscape’s Residents Lifestyle & Happiness Report 2023, a third of residents surveyed rarely or never paid attention to their well-being, which closely mirrors the 31% who rarely or never had time for a social life. Slightly more residents (37%) said their work-life balance was “somewhat worse” or “much worse” than they expected.
“I think everyone has burnout as a resident, regardless of the type of program they are in,” Dr. Whelihan said. He described the experience as when you lack fulfillment and empathy and feel exhausted, callous, and removed from interactions with colleagues and patients.
The American Medical Association’s recently released report on the state of residency well-being in 2023 also found that about 43% of residents and fellows had at least one symptom of burnout, about a 2% increase from 2022.
Efforts to Combat Burnout
One residency program found a way to reduce burnout by changing its block scheduling from 4 inpatient weeks followed by 1 outpatient week (4 + 1) to 4 inpatient call-based weeks and 4 outpatient ambulatory, non-call weeks (4 + 4), according to a survey study published recently in JAMA Network Open. The initiative drew praise from some residents and a med school professor who studies wellness issues.
In the survey of postgraduate year (PGY) 1 and PGY-2 hospitalist and primary care residents from the University of Colorado’s Internal Medicine Residency Program, Aurora, between June 2019 and June 2021, the schedule change resulted in improved burnout scores and self-reported professional, educational, and health benefits.
As part of the survey, residents rated symptoms on a 7-point scale on the basis of how frequently they experienced emotional exhaustion, depersonalization, and personal accomplishment.
Investigators also used a questionnaire to evaluate how participants perceived the rotation structure with various outcomes, including the ability to acquire clinical skills, access educational and scholarly opportunities, job satisfaction, and health.
The study concluded that the schedule change improved burnout, health, wellness, and professional development without weakening residents perceived clinical skills or standardized exam scores.
Still, the study authors acknowledged that several factors, including the pandemic, may have limited the findings. During that time, the study transitioned from in-person to electronic submissions, resulting in reduced response rates because of changes in staffing needs and fewer research and scholarly activities.
“One of the things we worried about was that the pandemic would make [burnout findings] look worse,” said lead author Dan Heppe, MD, a hospitalist and associate director of the CU Internal Medicine Residency Program. “Anecdotally, residents may have had more support in our program than perhaps some other programs. Though they had long hours with very sick patients, we tried to keep going in a positive direction.”
Dr. Heppe said in an interview that the purpose of the schedule change was to space out more intense rotations and build in more time for research, leadership, teaching, and professional development. He suggested the new schedule could help with other aspects of residents’ careers, exposing them to alternate avenues earlier in their training and in a more structured way.
Like most of the study authors, Dr. Heppe is a graduate of the residency program. He recalled how the program changed from multiple inpatient months in a row with clinic half days during those rotations to a 4 + 1 schedule. But the 1 week between inpatient rotations wasn’t enough time to recover or catch up on clinical work, said Dr. Heppe, who is also an associate professor of medicine at CU.
“It was too erratic,” he said of his former residency schedule. “There was a month of research here or there and clinic and then right back to the ICU for a couple of months without a break, and it was less predictable.”
Dr. Heppe said other residency programs have expressed interest in duplicating CU’s schedule change. He admits it may be difficult because of intensive schedule coordination, and some hospitals may not want to reduce clinical services.
The Yale Internal Medicine Traditional Residency Program also recently ended its 28-hour call, during which residents worked 24 hours with an additional 4 hours to transfer the patient to the incoming team. The move was made in response to residents’ requests, saying that the grueling call rotation’s time had come. The reaction has been overwhelmingly positive.
Proponents of alternate scheduling blocks [4 + 4 or 6 + 2] say that they improve residents’ educational experience, patient care, and continuity of care, reduce burnout, and guarantee residents time off.
Advancing Resident Well-Being
“The premise of looking at scheduling in a more intentional way is a sound one in the process of trying to support and advance resident well-being,” said Mark Greenawald, MD, vice chair of academic affairs, well-being, and professional development for the Virginia Tech Carilion School of Medicine’s Department of Family and Community Medicine in Roanoke.
He said it’s up to residency program directors or graduate medical education departments within a specialty to determine whether such scheduling changes fit their requirements for inpatient and outpatient care and training electives. Requirements may limit some scheduling changes, but within the specialty, there’s some flexibility to be creative with rotations. The CU study considered how to create a residency rhythm without stacking inpatient rotations so there’s recovery time.
“Human beings need a break. If residents work 80 hours continually, they will start to experience greater distress, which for many leads to burnout,” he said
Still, the study includes design flaws because it doesn’t explain how call times and hours differ between inpatient and outpatient rotations. “My own [family medicine] program also does outpatient clinics when we have inpatient service. We have half days in the clinic, which ensures better continuity care with the patient.”
Dr. Greenawald has yet to see much research published about the impact of resident schedule changes. By taking an experimental approach, the CU study showed that their particular change positively affected burnout. If the study leads to improvements in rotation schedules or encourages other programs to experiment with their schedules, it will be a step in the right direction.
How Residents Respond
Haidn Foster, MD, a third-year internal medicine resident at Penn State Health Milton S. Hershey Medical Center, Hershey, remembered experiencing burnout as an intern. At that time, he occasionally dealt with poor patient outcomes and sick patients while working long hours with only 1 day off each week. During a particularly challenging rotation, he felt overwhelmed and numb, which was exacerbated if a patient’s condition worsened or they passed away, he said.
His program follows a schedule of 6 weeks of inpatient training and 2 weeks of outpatient rotations (6 + 2). He said that restructuring residents’ schedules may be more effective than commonly used individual wellness modules, referring to the CU study. “The authors tried out a novel systematic way to tackle the epidemic of physician burnout overwhelming people in the medical community.”
Although the study found that schedule changes don’t affect standardized exam scores, Dr. Foster wondered about preceptor ratings, another marker for clinical competency.
He said future studies should attempt to change the structure of medical training delivery by evaluating models that best reduce burnout, are consistent with residents’ career goals, and produce competent physicians. “Burnout plagues our medical system and leads to too many physicians and physicians-in-training leaving the field or taking their lives. I’m not sure this particular mechanism gets us there, but it’s a step, and so that’s very important.”
Like Dr. Foster, Dr. Whelihan follows a 6 + 2 schedule. He said he would have welcomed a schedule that included more outpatient and less inpatient training and can see how changes in scheduling could reduce burnout. “More outpatient time gives you an opportunity to breathe. You get a little more time off working in clinic with less sick people at a slower pace.”
Ally Fuher, MD, said she chose CU’s Internal Medicine Residency Program 4 years ago largely because of its innovative schedule. Now the program’s chief medical resident, she knew the structure would give her more time to pursue other nonclinical interests including research and medical education, meet regularly with mentors, visit family in another state, and attend important life events.
She acknowledged that the alternative would have meant a more irregular schedule with the possibility of working as many as 80 hours a week on back-to-back inpatient rotations with only 1 day off a week, leaving minimal time to plan other activities, let alone rest and recover.
Dr. Fuher said a balanced schedule made her a more well-rounded person excited to engage in her profession. While she hasn’t personally experienced burnout, she realizes a schedule change may not completely solve the issue for others. However, it shows what progress programs can make when they create systemic structural change.
A version of this article first appeared on Medscape.com.
It’s the difference between running a marathon and taking a leisurely stroll. That’s how recent pediatrics resident Joey Whelihan, MD, compared an 11-hour inpatient hospital day with an 8-hour outpatient shift where residents see patients in a clinic.
With inpatient training, “you are lucky if you have time to cook dinner, go to bed, and get ready for the next day,” said Dr. Whelihan, who recently started his adolescent medicine fellowship at Children’s Hospital of Philadelphia after 3 years of residency there. Some residents have call every fourth day during inpatient rotations, working 24-28 hours at a time. They come in one morning and go home the next, he told this news organization.
“Outpatient blocks give you more time to catch your breath and feel somewhat refreshed and ready to take care of patients.”
Longer stretches of inpatient rotations are not sustainable, Dr. Whelihan added, and residents are likely to become exhausted. Fatigue is a leading cause of burnout, a mental, physical, and emotional challenge that residency programs and national medical organizations have been struggling to address.
In recent years, there has been a movement to reduce the maximum consecutive duration of resident duty hours in residency programs across the country. Fueled by resident health and patient safety concerns, the movement is a shift from the previous 24- to 36-hour call duty schedules.
Improved Call Systems = Better Residents
The connection between burnout, well-being, and work schedules appears regularly in national program standards. “Residents and faculty members are at risk for burnout and depression,” according to the current Accreditation Council for Graduate Medical Education’s standard residency program requirements.
“Programs, in partnership with their sponsoring institutions, have the same responsibility to address well-being as other aspects of resident competence,” the guidelines state. That charge includes “attention to scheduling, work intensity, and work compression that impacts resident well-being.”
In Medscape’s Residents Lifestyle & Happiness Report 2023, a third of residents surveyed rarely or never paid attention to their well-being, which closely mirrors the 31% who rarely or never had time for a social life. Slightly more residents (37%) said their work-life balance was “somewhat worse” or “much worse” than they expected.
“I think everyone has burnout as a resident, regardless of the type of program they are in,” Dr. Whelihan said. He described the experience as when you lack fulfillment and empathy and feel exhausted, callous, and removed from interactions with colleagues and patients.
The American Medical Association’s recently released report on the state of residency well-being in 2023 also found that about 43% of residents and fellows had at least one symptom of burnout, about a 2% increase from 2022.
Efforts to Combat Burnout
One residency program found a way to reduce burnout by changing its block scheduling from 4 inpatient weeks followed by 1 outpatient week (4 + 1) to 4 inpatient call-based weeks and 4 outpatient ambulatory, non-call weeks (4 + 4), according to a survey study published recently in JAMA Network Open. The initiative drew praise from some residents and a med school professor who studies wellness issues.
In the survey of postgraduate year (PGY) 1 and PGY-2 hospitalist and primary care residents from the University of Colorado’s Internal Medicine Residency Program, Aurora, between June 2019 and June 2021, the schedule change resulted in improved burnout scores and self-reported professional, educational, and health benefits.
As part of the survey, residents rated symptoms on a 7-point scale on the basis of how frequently they experienced emotional exhaustion, depersonalization, and personal accomplishment.
Investigators also used a questionnaire to evaluate how participants perceived the rotation structure with various outcomes, including the ability to acquire clinical skills, access educational and scholarly opportunities, job satisfaction, and health.
The study concluded that the schedule change improved burnout, health, wellness, and professional development without weakening residents perceived clinical skills or standardized exam scores.
Still, the study authors acknowledged that several factors, including the pandemic, may have limited the findings. During that time, the study transitioned from in-person to electronic submissions, resulting in reduced response rates because of changes in staffing needs and fewer research and scholarly activities.
“One of the things we worried about was that the pandemic would make [burnout findings] look worse,” said lead author Dan Heppe, MD, a hospitalist and associate director of the CU Internal Medicine Residency Program. “Anecdotally, residents may have had more support in our program than perhaps some other programs. Though they had long hours with very sick patients, we tried to keep going in a positive direction.”
Dr. Heppe said in an interview that the purpose of the schedule change was to space out more intense rotations and build in more time for research, leadership, teaching, and professional development. He suggested the new schedule could help with other aspects of residents’ careers, exposing them to alternate avenues earlier in their training and in a more structured way.
Like most of the study authors, Dr. Heppe is a graduate of the residency program. He recalled how the program changed from multiple inpatient months in a row with clinic half days during those rotations to a 4 + 1 schedule. But the 1 week between inpatient rotations wasn’t enough time to recover or catch up on clinical work, said Dr. Heppe, who is also an associate professor of medicine at CU.
“It was too erratic,” he said of his former residency schedule. “There was a month of research here or there and clinic and then right back to the ICU for a couple of months without a break, and it was less predictable.”
Dr. Heppe said other residency programs have expressed interest in duplicating CU’s schedule change. He admits it may be difficult because of intensive schedule coordination, and some hospitals may not want to reduce clinical services.
The Yale Internal Medicine Traditional Residency Program also recently ended its 28-hour call, during which residents worked 24 hours with an additional 4 hours to transfer the patient to the incoming team. The move was made in response to residents’ requests, saying that the grueling call rotation’s time had come. The reaction has been overwhelmingly positive.
Proponents of alternate scheduling blocks [4 + 4 or 6 + 2] say that they improve residents’ educational experience, patient care, and continuity of care, reduce burnout, and guarantee residents time off.
Advancing Resident Well-Being
“The premise of looking at scheduling in a more intentional way is a sound one in the process of trying to support and advance resident well-being,” said Mark Greenawald, MD, vice chair of academic affairs, well-being, and professional development for the Virginia Tech Carilion School of Medicine’s Department of Family and Community Medicine in Roanoke.
He said it’s up to residency program directors or graduate medical education departments within a specialty to determine whether such scheduling changes fit their requirements for inpatient and outpatient care and training electives. Requirements may limit some scheduling changes, but within the specialty, there’s some flexibility to be creative with rotations. The CU study considered how to create a residency rhythm without stacking inpatient rotations so there’s recovery time.
“Human beings need a break. If residents work 80 hours continually, they will start to experience greater distress, which for many leads to burnout,” he said
Still, the study includes design flaws because it doesn’t explain how call times and hours differ between inpatient and outpatient rotations. “My own [family medicine] program also does outpatient clinics when we have inpatient service. We have half days in the clinic, which ensures better continuity care with the patient.”
Dr. Greenawald has yet to see much research published about the impact of resident schedule changes. By taking an experimental approach, the CU study showed that their particular change positively affected burnout. If the study leads to improvements in rotation schedules or encourages other programs to experiment with their schedules, it will be a step in the right direction.
How Residents Respond
Haidn Foster, MD, a third-year internal medicine resident at Penn State Health Milton S. Hershey Medical Center, Hershey, remembered experiencing burnout as an intern. At that time, he occasionally dealt with poor patient outcomes and sick patients while working long hours with only 1 day off each week. During a particularly challenging rotation, he felt overwhelmed and numb, which was exacerbated if a patient’s condition worsened or they passed away, he said.
His program follows a schedule of 6 weeks of inpatient training and 2 weeks of outpatient rotations (6 + 2). He said that restructuring residents’ schedules may be more effective than commonly used individual wellness modules, referring to the CU study. “The authors tried out a novel systematic way to tackle the epidemic of physician burnout overwhelming people in the medical community.”
Although the study found that schedule changes don’t affect standardized exam scores, Dr. Foster wondered about preceptor ratings, another marker for clinical competency.
He said future studies should attempt to change the structure of medical training delivery by evaluating models that best reduce burnout, are consistent with residents’ career goals, and produce competent physicians. “Burnout plagues our medical system and leads to too many physicians and physicians-in-training leaving the field or taking their lives. I’m not sure this particular mechanism gets us there, but it’s a step, and so that’s very important.”
Like Dr. Foster, Dr. Whelihan follows a 6 + 2 schedule. He said he would have welcomed a schedule that included more outpatient and less inpatient training and can see how changes in scheduling could reduce burnout. “More outpatient time gives you an opportunity to breathe. You get a little more time off working in clinic with less sick people at a slower pace.”
Ally Fuher, MD, said she chose CU’s Internal Medicine Residency Program 4 years ago largely because of its innovative schedule. Now the program’s chief medical resident, she knew the structure would give her more time to pursue other nonclinical interests including research and medical education, meet regularly with mentors, visit family in another state, and attend important life events.
She acknowledged that the alternative would have meant a more irregular schedule with the possibility of working as many as 80 hours a week on back-to-back inpatient rotations with only 1 day off a week, leaving minimal time to plan other activities, let alone rest and recover.
Dr. Fuher said a balanced schedule made her a more well-rounded person excited to engage in her profession. While she hasn’t personally experienced burnout, she realizes a schedule change may not completely solve the issue for others. However, it shows what progress programs can make when they create systemic structural change.
A version of this article first appeared on Medscape.com.
It’s the difference between running a marathon and taking a leisurely stroll. That’s how recent pediatrics resident Joey Whelihan, MD, compared an 11-hour inpatient hospital day with an 8-hour outpatient shift where residents see patients in a clinic.
With inpatient training, “you are lucky if you have time to cook dinner, go to bed, and get ready for the next day,” said Dr. Whelihan, who recently started his adolescent medicine fellowship at Children’s Hospital of Philadelphia after 3 years of residency there. Some residents have call every fourth day during inpatient rotations, working 24-28 hours at a time. They come in one morning and go home the next, he told this news organization.
“Outpatient blocks give you more time to catch your breath and feel somewhat refreshed and ready to take care of patients.”
Longer stretches of inpatient rotations are not sustainable, Dr. Whelihan added, and residents are likely to become exhausted. Fatigue is a leading cause of burnout, a mental, physical, and emotional challenge that residency programs and national medical organizations have been struggling to address.
In recent years, there has been a movement to reduce the maximum consecutive duration of resident duty hours in residency programs across the country. Fueled by resident health and patient safety concerns, the movement is a shift from the previous 24- to 36-hour call duty schedules.
Improved Call Systems = Better Residents
The connection between burnout, well-being, and work schedules appears regularly in national program standards. “Residents and faculty members are at risk for burnout and depression,” according to the current Accreditation Council for Graduate Medical Education’s standard residency program requirements.
“Programs, in partnership with their sponsoring institutions, have the same responsibility to address well-being as other aspects of resident competence,” the guidelines state. That charge includes “attention to scheduling, work intensity, and work compression that impacts resident well-being.”
In Medscape’s Residents Lifestyle & Happiness Report 2023, a third of residents surveyed rarely or never paid attention to their well-being, which closely mirrors the 31% who rarely or never had time for a social life. Slightly more residents (37%) said their work-life balance was “somewhat worse” or “much worse” than they expected.
“I think everyone has burnout as a resident, regardless of the type of program they are in,” Dr. Whelihan said. He described the experience as when you lack fulfillment and empathy and feel exhausted, callous, and removed from interactions with colleagues and patients.
The American Medical Association’s recently released report on the state of residency well-being in 2023 also found that about 43% of residents and fellows had at least one symptom of burnout, about a 2% increase from 2022.
Efforts to Combat Burnout
One residency program found a way to reduce burnout by changing its block scheduling from 4 inpatient weeks followed by 1 outpatient week (4 + 1) to 4 inpatient call-based weeks and 4 outpatient ambulatory, non-call weeks (4 + 4), according to a survey study published recently in JAMA Network Open. The initiative drew praise from some residents and a med school professor who studies wellness issues.
In the survey of postgraduate year (PGY) 1 and PGY-2 hospitalist and primary care residents from the University of Colorado’s Internal Medicine Residency Program, Aurora, between June 2019 and June 2021, the schedule change resulted in improved burnout scores and self-reported professional, educational, and health benefits.
As part of the survey, residents rated symptoms on a 7-point scale on the basis of how frequently they experienced emotional exhaustion, depersonalization, and personal accomplishment.
Investigators also used a questionnaire to evaluate how participants perceived the rotation structure with various outcomes, including the ability to acquire clinical skills, access educational and scholarly opportunities, job satisfaction, and health.
The study concluded that the schedule change improved burnout, health, wellness, and professional development without weakening residents perceived clinical skills or standardized exam scores.
Still, the study authors acknowledged that several factors, including the pandemic, may have limited the findings. During that time, the study transitioned from in-person to electronic submissions, resulting in reduced response rates because of changes in staffing needs and fewer research and scholarly activities.
“One of the things we worried about was that the pandemic would make [burnout findings] look worse,” said lead author Dan Heppe, MD, a hospitalist and associate director of the CU Internal Medicine Residency Program. “Anecdotally, residents may have had more support in our program than perhaps some other programs. Though they had long hours with very sick patients, we tried to keep going in a positive direction.”
Dr. Heppe said in an interview that the purpose of the schedule change was to space out more intense rotations and build in more time for research, leadership, teaching, and professional development. He suggested the new schedule could help with other aspects of residents’ careers, exposing them to alternate avenues earlier in their training and in a more structured way.
Like most of the study authors, Dr. Heppe is a graduate of the residency program. He recalled how the program changed from multiple inpatient months in a row with clinic half days during those rotations to a 4 + 1 schedule. But the 1 week between inpatient rotations wasn’t enough time to recover or catch up on clinical work, said Dr. Heppe, who is also an associate professor of medicine at CU.
“It was too erratic,” he said of his former residency schedule. “There was a month of research here or there and clinic and then right back to the ICU for a couple of months without a break, and it was less predictable.”
Dr. Heppe said other residency programs have expressed interest in duplicating CU’s schedule change. He admits it may be difficult because of intensive schedule coordination, and some hospitals may not want to reduce clinical services.
The Yale Internal Medicine Traditional Residency Program also recently ended its 28-hour call, during which residents worked 24 hours with an additional 4 hours to transfer the patient to the incoming team. The move was made in response to residents’ requests, saying that the grueling call rotation’s time had come. The reaction has been overwhelmingly positive.
Proponents of alternate scheduling blocks [4 + 4 or 6 + 2] say that they improve residents’ educational experience, patient care, and continuity of care, reduce burnout, and guarantee residents time off.
Advancing Resident Well-Being
“The premise of looking at scheduling in a more intentional way is a sound one in the process of trying to support and advance resident well-being,” said Mark Greenawald, MD, vice chair of academic affairs, well-being, and professional development for the Virginia Tech Carilion School of Medicine’s Department of Family and Community Medicine in Roanoke.
He said it’s up to residency program directors or graduate medical education departments within a specialty to determine whether such scheduling changes fit their requirements for inpatient and outpatient care and training electives. Requirements may limit some scheduling changes, but within the specialty, there’s some flexibility to be creative with rotations. The CU study considered how to create a residency rhythm without stacking inpatient rotations so there’s recovery time.
“Human beings need a break. If residents work 80 hours continually, they will start to experience greater distress, which for many leads to burnout,” he said
Still, the study includes design flaws because it doesn’t explain how call times and hours differ between inpatient and outpatient rotations. “My own [family medicine] program also does outpatient clinics when we have inpatient service. We have half days in the clinic, which ensures better continuity care with the patient.”
Dr. Greenawald has yet to see much research published about the impact of resident schedule changes. By taking an experimental approach, the CU study showed that their particular change positively affected burnout. If the study leads to improvements in rotation schedules or encourages other programs to experiment with their schedules, it will be a step in the right direction.
How Residents Respond
Haidn Foster, MD, a third-year internal medicine resident at Penn State Health Milton S. Hershey Medical Center, Hershey, remembered experiencing burnout as an intern. At that time, he occasionally dealt with poor patient outcomes and sick patients while working long hours with only 1 day off each week. During a particularly challenging rotation, he felt overwhelmed and numb, which was exacerbated if a patient’s condition worsened or they passed away, he said.
His program follows a schedule of 6 weeks of inpatient training and 2 weeks of outpatient rotations (6 + 2). He said that restructuring residents’ schedules may be more effective than commonly used individual wellness modules, referring to the CU study. “The authors tried out a novel systematic way to tackle the epidemic of physician burnout overwhelming people in the medical community.”
Although the study found that schedule changes don’t affect standardized exam scores, Dr. Foster wondered about preceptor ratings, another marker for clinical competency.
He said future studies should attempt to change the structure of medical training delivery by evaluating models that best reduce burnout, are consistent with residents’ career goals, and produce competent physicians. “Burnout plagues our medical system and leads to too many physicians and physicians-in-training leaving the field or taking their lives. I’m not sure this particular mechanism gets us there, but it’s a step, and so that’s very important.”
Like Dr. Foster, Dr. Whelihan follows a 6 + 2 schedule. He said he would have welcomed a schedule that included more outpatient and less inpatient training and can see how changes in scheduling could reduce burnout. “More outpatient time gives you an opportunity to breathe. You get a little more time off working in clinic with less sick people at a slower pace.”
Ally Fuher, MD, said she chose CU’s Internal Medicine Residency Program 4 years ago largely because of its innovative schedule. Now the program’s chief medical resident, she knew the structure would give her more time to pursue other nonclinical interests including research and medical education, meet regularly with mentors, visit family in another state, and attend important life events.
She acknowledged that the alternative would have meant a more irregular schedule with the possibility of working as many as 80 hours a week on back-to-back inpatient rotations with only 1 day off a week, leaving minimal time to plan other activities, let alone rest and recover.
Dr. Fuher said a balanced schedule made her a more well-rounded person excited to engage in her profession. While she hasn’t personally experienced burnout, she realizes a schedule change may not completely solve the issue for others. However, it shows what progress programs can make when they create systemic structural change.
A version of this article first appeared on Medscape.com.
Penalty for No-Shows?
Earlier in 2024 the French government proposed fining patients €5 ($5.36 at the time of writing) for no-show doctor appointments.
The rationale is that there are 27 million missed medical appointments annually in France (just based on population size, I’d guess it’s higher in the United States) and that they not only waste time, but also keep people who need to be seen sooner from getting in.
The penalty wouldn’t be automatic, and it’s up to the physician to decide if a patient’s excuse is valid. As I understand it, the €5 is paid as a fine to the national healthcare service, and not to the physician (I may be wrong on that).
In many ways I agree with this. Given the patchwork of regulations and insurance rules we face in the United States, it’s almost impossible to penalize patients for missed visits unless you don’t take insurance at all.
Some people have legitimate reasons for no-showing. Cars break, family emergencies happen, storms roll in. Even the most punctual of us sometimes just space on something. If someone calls in at the last minute to say “I can’t make it” I’m more forgiving than if we never hear from them at all. That’s why it’s good to have the doctors, who know the people they’re dealing with, make the final call.
Of course, there are those who will just lie and make up an excuse, and sometimes it’s tricky to know who is or isn’t worth penalizing. Some people just don’t care, or are dishonest, or both.
$5.36 isn’t a huge amount for most. But it’s still symbolic. It forces people to, as they say, “have skin in the game.” Yes, they may still have a copay, but that’s only paid if they show up. This puts them in the position of being penalized for thoughtlessness.
Is it a great idea? Not really. I suspect most of us would dismiss it rather than fight with the patient.
But there aren’t any easy answers, and I’d like to see how, if they go ahead with the proposal, it plays out. If it works, I hope we won’t be too far behind.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Earlier in 2024 the French government proposed fining patients €5 ($5.36 at the time of writing) for no-show doctor appointments.
The rationale is that there are 27 million missed medical appointments annually in France (just based on population size, I’d guess it’s higher in the United States) and that they not only waste time, but also keep people who need to be seen sooner from getting in.
The penalty wouldn’t be automatic, and it’s up to the physician to decide if a patient’s excuse is valid. As I understand it, the €5 is paid as a fine to the national healthcare service, and not to the physician (I may be wrong on that).
In many ways I agree with this. Given the patchwork of regulations and insurance rules we face in the United States, it’s almost impossible to penalize patients for missed visits unless you don’t take insurance at all.
Some people have legitimate reasons for no-showing. Cars break, family emergencies happen, storms roll in. Even the most punctual of us sometimes just space on something. If someone calls in at the last minute to say “I can’t make it” I’m more forgiving than if we never hear from them at all. That’s why it’s good to have the doctors, who know the people they’re dealing with, make the final call.
Of course, there are those who will just lie and make up an excuse, and sometimes it’s tricky to know who is or isn’t worth penalizing. Some people just don’t care, or are dishonest, or both.
$5.36 isn’t a huge amount for most. But it’s still symbolic. It forces people to, as they say, “have skin in the game.” Yes, they may still have a copay, but that’s only paid if they show up. This puts them in the position of being penalized for thoughtlessness.
Is it a great idea? Not really. I suspect most of us would dismiss it rather than fight with the patient.
But there aren’t any easy answers, and I’d like to see how, if they go ahead with the proposal, it plays out. If it works, I hope we won’t be too far behind.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Earlier in 2024 the French government proposed fining patients €5 ($5.36 at the time of writing) for no-show doctor appointments.
The rationale is that there are 27 million missed medical appointments annually in France (just based on population size, I’d guess it’s higher in the United States) and that they not only waste time, but also keep people who need to be seen sooner from getting in.
The penalty wouldn’t be automatic, and it’s up to the physician to decide if a patient’s excuse is valid. As I understand it, the €5 is paid as a fine to the national healthcare service, and not to the physician (I may be wrong on that).
In many ways I agree with this. Given the patchwork of regulations and insurance rules we face in the United States, it’s almost impossible to penalize patients for missed visits unless you don’t take insurance at all.
Some people have legitimate reasons for no-showing. Cars break, family emergencies happen, storms roll in. Even the most punctual of us sometimes just space on something. If someone calls in at the last minute to say “I can’t make it” I’m more forgiving than if we never hear from them at all. That’s why it’s good to have the doctors, who know the people they’re dealing with, make the final call.
Of course, there are those who will just lie and make up an excuse, and sometimes it’s tricky to know who is or isn’t worth penalizing. Some people just don’t care, or are dishonest, or both.
$5.36 isn’t a huge amount for most. But it’s still symbolic. It forces people to, as they say, “have skin in the game.” Yes, they may still have a copay, but that’s only paid if they show up. This puts them in the position of being penalized for thoughtlessness.
Is it a great idea? Not really. I suspect most of us would dismiss it rather than fight with the patient.
But there aren’t any easy answers, and I’d like to see how, if they go ahead with the proposal, it plays out. If it works, I hope we won’t be too far behind.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Guidance on How Best to Manage Opioid Risks in Older Adults
Polypharmacy and slow metabolism of drugs create a high risk among older adults for substance use disorder, raising the odds of intentional and unintentional overdoses. However, screening, assessment, and treatment for substance use disorder occurs less often in younger adults.
Rates of overdose from opioids increased the most among people aged 65 years and older from 2021 to 2022, compared with among younger age groups. Meanwhile, recent data show less than half older adults with opioid use disorder (OUD) receive care for the condition.
“Nobody is immune to developing some kind of use disorder, so don’t just assume that because someone’s 80 years old that there’s no way that they have a problem,” said Sara Meyer, PharmD, a medication safety pharmacist at Novant Health in Winston-Salem, North Carolina. “You never know who’s going to potentially have an issue.”
in an effort to reduce addiction and overdoses.
Older Adults Have Unique Needs
A major challenge of treating older adults is their high incidence of chronic pain and multiple complex chronic conditions. As a result, some of the nonopioid medications clinicians might otherwise prescribe, like nonsteroidal anti-inflammatory drugs, cannot be used, according to Caroline Goldzweig, MD, chief medical officer of the Cedars-Sinai Medical Network in Los Angeles, California.
“Before you know it, the only thing left is an opiate, so you can sometimes be between a rock and a hard place,” she said.
But for adults older than 65 years, opioids can carry problematic side effects, including sedation, cognitive impairment, falls, and fractures.
With those factors in mind, part of a yearly checkup or wellness visit should include time to discuss how a patient is managing their chronic pain, according to Timothy Anderson, MD, an assistant professor of medicine at the University of Pittsburgh, Pittsburgh, Pennsylvania, and codirector of the Prescribing Wisely Lab, a research collaboration between that institution and Beth Israel Deaconess Medical Center in Boston.
When considering a prescription for pain medication, Dr. Anderson said he evaluates the potential worst, best, and average outcomes for a patient. Nonopioid options should always be considered first-line treatment. Patients and physicians often struggle with balancing an option that meets a patient’s goals for pain relief but does not put them at a risk for adverse outcomes, he said.
Greater Risk
Older adults experience neurophysiologic effects different from younger people, said Benjamin Han, MD, a geriatrician and addiction medicine specialist at the University of California, San Diego.
Seniors also absorb, metabolize, and excrete drugs differently, sometimes affected by decreased production of gastric acid, lean body mass, and renal function. Coupled with complications of other chronic conditions or medications, diagnosing problematic opioid use or OUD can be one of the most challenging experiences in geriatrics, Dr. Han said.
As a result, OUD is often underdiagnosed in these patients, he said. Single-item screening tools like the TAPS and OWLS can be used to assess if the benefits of an opioid outweigh a patient’s risk for addiction.
Dr. Han finds medications like buprenorphine to be relatively safe and effective, along with nonpharmacologic interventions like physical therapy. He also advised clinicians to provide patients with opioid-overdose reversal agents.
“Naloxone is only used for reversing opioid withdrawal, but it is important to ensure that any patient at risk for an overdose, including being on chronic opioids, is provided naloxone and educated on preventing opioid overdoses,” he said.
Steroid injections and medications that target specific pathways, such as neuropathic pain, can be helpful in primary care for these older patients, according to Pooja Lagisetty, MD, an internal medicine physician at Michigan Medicine and a research scientist at VA Ann Arbor Health Care, Ann Arbor, Michigan.
She often recommends to her patients online programs that help them maintain strength and mobility, as well as low-impact exercises like tai chi, for pain management.
“This will ensure a much more balanced, patient-centered conversation with whatever decisions you and your patient come to,” Dr. Lagisetty said.
New Protocols for Pain Management in Older Adults
At the health system level, clinicians can use treatment agreements for patients taking opioids. At Novant, patients must attest they agree to take the medications only as prescribed and from a specified pharmacy. They promise not to seek opioids from other sources, to submit to random drug screenings, and to communicate regularly with their clinician about any health issues.
If a patient violates any part of this agreement, their clinician can stop the treatment. The system encourages clinicians to help patients find additional care for substance abuse disorder or pain management if it occurs.
Over the past 2 years, Novant also developed an AI prediction model, which generates a score for the risk a patient has in developing substance use disorder or experiencing an overdose within a year of initial opioid prescription. The model was validated by an internal team at the system but has not been independently certified.
If a patient has a high-risk score, their clinician considers additional risk mitigation strategies, such as seeing the patient more frequently or using an abuse deterrent formulation of an opioid. They also have the option of referring the patient to specialists in addiction medicine or neurology. Opioids are not necessarily withheld, according to Dr. Meyer. The tool is now used by clinicians during Medicare annual wellness visits.
And coming later this year are new protocols for pain management in patients aged 80 years and older. Clinicians will target a 50% dose reduction, compared with what a younger patient might receive to account for physiologic differences.
“We know that especially with some opioids like morphine, they’re not going to metabolize that the same way a young person with a young kidney will, so we’re trying to set the clinician up to select a lower starting dose for patients that are older,” Dr. Meyer said.
In 2017, the system implemented a program to reduce prescription of opioids to less than 350 morphine milligram equivalents (MME) per order following any kind of surgery. The health system compared numbers of prescriptions written among surgical colleagues and met with them to discuss alternative approaches. Novant said it continues to monitor the data and follow-up with surgeons who are not in alignment with the goal.
Between 2017 and 2019, patients switching to lower doses after surgeries rose by 20%.
Across the country at Cedars-Sinai Medical Network, leadership in 2016 made the move to deprescribe opioids or lower doses of the drugs to less than 90 MME per day, in accordance with Centers for Disease Control and Prevention guidelines established that year. Patients were referred to their pain program for support and for nonopioid interventions. Pharmacists worked closely with clinicians on safely tapering these medications in patients taking high doses.
The program worked, according to Dr. Goldzweig. Dr. Goldzweig could only find two patients currently taking high-dose opioids in the system’s database out of more than 7000 patients with Medicare Advantage insurance coverage.
“There will always be some patients who have no alternative than opioids, but we established some discipline with urine tox screens and pain agreements, and over time, we’ve been able to reduce the number of high-risk opioid prescriptions,” she said.
A version of this article first appeared on Medscape.com.
Polypharmacy and slow metabolism of drugs create a high risk among older adults for substance use disorder, raising the odds of intentional and unintentional overdoses. However, screening, assessment, and treatment for substance use disorder occurs less often in younger adults.
Rates of overdose from opioids increased the most among people aged 65 years and older from 2021 to 2022, compared with among younger age groups. Meanwhile, recent data show less than half older adults with opioid use disorder (OUD) receive care for the condition.
“Nobody is immune to developing some kind of use disorder, so don’t just assume that because someone’s 80 years old that there’s no way that they have a problem,” said Sara Meyer, PharmD, a medication safety pharmacist at Novant Health in Winston-Salem, North Carolina. “You never know who’s going to potentially have an issue.”
in an effort to reduce addiction and overdoses.
Older Adults Have Unique Needs
A major challenge of treating older adults is their high incidence of chronic pain and multiple complex chronic conditions. As a result, some of the nonopioid medications clinicians might otherwise prescribe, like nonsteroidal anti-inflammatory drugs, cannot be used, according to Caroline Goldzweig, MD, chief medical officer of the Cedars-Sinai Medical Network in Los Angeles, California.
“Before you know it, the only thing left is an opiate, so you can sometimes be between a rock and a hard place,” she said.
But for adults older than 65 years, opioids can carry problematic side effects, including sedation, cognitive impairment, falls, and fractures.
With those factors in mind, part of a yearly checkup or wellness visit should include time to discuss how a patient is managing their chronic pain, according to Timothy Anderson, MD, an assistant professor of medicine at the University of Pittsburgh, Pittsburgh, Pennsylvania, and codirector of the Prescribing Wisely Lab, a research collaboration between that institution and Beth Israel Deaconess Medical Center in Boston.
When considering a prescription for pain medication, Dr. Anderson said he evaluates the potential worst, best, and average outcomes for a patient. Nonopioid options should always be considered first-line treatment. Patients and physicians often struggle with balancing an option that meets a patient’s goals for pain relief but does not put them at a risk for adverse outcomes, he said.
Greater Risk
Older adults experience neurophysiologic effects different from younger people, said Benjamin Han, MD, a geriatrician and addiction medicine specialist at the University of California, San Diego.
Seniors also absorb, metabolize, and excrete drugs differently, sometimes affected by decreased production of gastric acid, lean body mass, and renal function. Coupled with complications of other chronic conditions or medications, diagnosing problematic opioid use or OUD can be one of the most challenging experiences in geriatrics, Dr. Han said.
As a result, OUD is often underdiagnosed in these patients, he said. Single-item screening tools like the TAPS and OWLS can be used to assess if the benefits of an opioid outweigh a patient’s risk for addiction.
Dr. Han finds medications like buprenorphine to be relatively safe and effective, along with nonpharmacologic interventions like physical therapy. He also advised clinicians to provide patients with opioid-overdose reversal agents.
“Naloxone is only used for reversing opioid withdrawal, but it is important to ensure that any patient at risk for an overdose, including being on chronic opioids, is provided naloxone and educated on preventing opioid overdoses,” he said.
Steroid injections and medications that target specific pathways, such as neuropathic pain, can be helpful in primary care for these older patients, according to Pooja Lagisetty, MD, an internal medicine physician at Michigan Medicine and a research scientist at VA Ann Arbor Health Care, Ann Arbor, Michigan.
She often recommends to her patients online programs that help them maintain strength and mobility, as well as low-impact exercises like tai chi, for pain management.
“This will ensure a much more balanced, patient-centered conversation with whatever decisions you and your patient come to,” Dr. Lagisetty said.
New Protocols for Pain Management in Older Adults
At the health system level, clinicians can use treatment agreements for patients taking opioids. At Novant, patients must attest they agree to take the medications only as prescribed and from a specified pharmacy. They promise not to seek opioids from other sources, to submit to random drug screenings, and to communicate regularly with their clinician about any health issues.
If a patient violates any part of this agreement, their clinician can stop the treatment. The system encourages clinicians to help patients find additional care for substance abuse disorder or pain management if it occurs.
Over the past 2 years, Novant also developed an AI prediction model, which generates a score for the risk a patient has in developing substance use disorder or experiencing an overdose within a year of initial opioid prescription. The model was validated by an internal team at the system but has not been independently certified.
If a patient has a high-risk score, their clinician considers additional risk mitigation strategies, such as seeing the patient more frequently or using an abuse deterrent formulation of an opioid. They also have the option of referring the patient to specialists in addiction medicine or neurology. Opioids are not necessarily withheld, according to Dr. Meyer. The tool is now used by clinicians during Medicare annual wellness visits.
And coming later this year are new protocols for pain management in patients aged 80 years and older. Clinicians will target a 50% dose reduction, compared with what a younger patient might receive to account for physiologic differences.
“We know that especially with some opioids like morphine, they’re not going to metabolize that the same way a young person with a young kidney will, so we’re trying to set the clinician up to select a lower starting dose for patients that are older,” Dr. Meyer said.
In 2017, the system implemented a program to reduce prescription of opioids to less than 350 morphine milligram equivalents (MME) per order following any kind of surgery. The health system compared numbers of prescriptions written among surgical colleagues and met with them to discuss alternative approaches. Novant said it continues to monitor the data and follow-up with surgeons who are not in alignment with the goal.
Between 2017 and 2019, patients switching to lower doses after surgeries rose by 20%.
Across the country at Cedars-Sinai Medical Network, leadership in 2016 made the move to deprescribe opioids or lower doses of the drugs to less than 90 MME per day, in accordance with Centers for Disease Control and Prevention guidelines established that year. Patients were referred to their pain program for support and for nonopioid interventions. Pharmacists worked closely with clinicians on safely tapering these medications in patients taking high doses.
The program worked, according to Dr. Goldzweig. Dr. Goldzweig could only find two patients currently taking high-dose opioids in the system’s database out of more than 7000 patients with Medicare Advantage insurance coverage.
“There will always be some patients who have no alternative than opioids, but we established some discipline with urine tox screens and pain agreements, and over time, we’ve been able to reduce the number of high-risk opioid prescriptions,” she said.
A version of this article first appeared on Medscape.com.
Polypharmacy and slow metabolism of drugs create a high risk among older adults for substance use disorder, raising the odds of intentional and unintentional overdoses. However, screening, assessment, and treatment for substance use disorder occurs less often in younger adults.
Rates of overdose from opioids increased the most among people aged 65 years and older from 2021 to 2022, compared with among younger age groups. Meanwhile, recent data show less than half older adults with opioid use disorder (OUD) receive care for the condition.
“Nobody is immune to developing some kind of use disorder, so don’t just assume that because someone’s 80 years old that there’s no way that they have a problem,” said Sara Meyer, PharmD, a medication safety pharmacist at Novant Health in Winston-Salem, North Carolina. “You never know who’s going to potentially have an issue.”
in an effort to reduce addiction and overdoses.
Older Adults Have Unique Needs
A major challenge of treating older adults is their high incidence of chronic pain and multiple complex chronic conditions. As a result, some of the nonopioid medications clinicians might otherwise prescribe, like nonsteroidal anti-inflammatory drugs, cannot be used, according to Caroline Goldzweig, MD, chief medical officer of the Cedars-Sinai Medical Network in Los Angeles, California.
“Before you know it, the only thing left is an opiate, so you can sometimes be between a rock and a hard place,” she said.
But for adults older than 65 years, opioids can carry problematic side effects, including sedation, cognitive impairment, falls, and fractures.
With those factors in mind, part of a yearly checkup or wellness visit should include time to discuss how a patient is managing their chronic pain, according to Timothy Anderson, MD, an assistant professor of medicine at the University of Pittsburgh, Pittsburgh, Pennsylvania, and codirector of the Prescribing Wisely Lab, a research collaboration between that institution and Beth Israel Deaconess Medical Center in Boston.
When considering a prescription for pain medication, Dr. Anderson said he evaluates the potential worst, best, and average outcomes for a patient. Nonopioid options should always be considered first-line treatment. Patients and physicians often struggle with balancing an option that meets a patient’s goals for pain relief but does not put them at a risk for adverse outcomes, he said.
Greater Risk
Older adults experience neurophysiologic effects different from younger people, said Benjamin Han, MD, a geriatrician and addiction medicine specialist at the University of California, San Diego.
Seniors also absorb, metabolize, and excrete drugs differently, sometimes affected by decreased production of gastric acid, lean body mass, and renal function. Coupled with complications of other chronic conditions or medications, diagnosing problematic opioid use or OUD can be one of the most challenging experiences in geriatrics, Dr. Han said.
As a result, OUD is often underdiagnosed in these patients, he said. Single-item screening tools like the TAPS and OWLS can be used to assess if the benefits of an opioid outweigh a patient’s risk for addiction.
Dr. Han finds medications like buprenorphine to be relatively safe and effective, along with nonpharmacologic interventions like physical therapy. He also advised clinicians to provide patients with opioid-overdose reversal agents.
“Naloxone is only used for reversing opioid withdrawal, but it is important to ensure that any patient at risk for an overdose, including being on chronic opioids, is provided naloxone and educated on preventing opioid overdoses,” he said.
Steroid injections and medications that target specific pathways, such as neuropathic pain, can be helpful in primary care for these older patients, according to Pooja Lagisetty, MD, an internal medicine physician at Michigan Medicine and a research scientist at VA Ann Arbor Health Care, Ann Arbor, Michigan.
She often recommends to her patients online programs that help them maintain strength and mobility, as well as low-impact exercises like tai chi, for pain management.
“This will ensure a much more balanced, patient-centered conversation with whatever decisions you and your patient come to,” Dr. Lagisetty said.
New Protocols for Pain Management in Older Adults
At the health system level, clinicians can use treatment agreements for patients taking opioids. At Novant, patients must attest they agree to take the medications only as prescribed and from a specified pharmacy. They promise not to seek opioids from other sources, to submit to random drug screenings, and to communicate regularly with their clinician about any health issues.
If a patient violates any part of this agreement, their clinician can stop the treatment. The system encourages clinicians to help patients find additional care for substance abuse disorder or pain management if it occurs.
Over the past 2 years, Novant also developed an AI prediction model, which generates a score for the risk a patient has in developing substance use disorder or experiencing an overdose within a year of initial opioid prescription. The model was validated by an internal team at the system but has not been independently certified.
If a patient has a high-risk score, their clinician considers additional risk mitigation strategies, such as seeing the patient more frequently or using an abuse deterrent formulation of an opioid. They also have the option of referring the patient to specialists in addiction medicine or neurology. Opioids are not necessarily withheld, according to Dr. Meyer. The tool is now used by clinicians during Medicare annual wellness visits.
And coming later this year are new protocols for pain management in patients aged 80 years and older. Clinicians will target a 50% dose reduction, compared with what a younger patient might receive to account for physiologic differences.
“We know that especially with some opioids like morphine, they’re not going to metabolize that the same way a young person with a young kidney will, so we’re trying to set the clinician up to select a lower starting dose for patients that are older,” Dr. Meyer said.
In 2017, the system implemented a program to reduce prescription of opioids to less than 350 morphine milligram equivalents (MME) per order following any kind of surgery. The health system compared numbers of prescriptions written among surgical colleagues and met with them to discuss alternative approaches. Novant said it continues to monitor the data and follow-up with surgeons who are not in alignment with the goal.
Between 2017 and 2019, patients switching to lower doses after surgeries rose by 20%.
Across the country at Cedars-Sinai Medical Network, leadership in 2016 made the move to deprescribe opioids or lower doses of the drugs to less than 90 MME per day, in accordance with Centers for Disease Control and Prevention guidelines established that year. Patients were referred to their pain program for support and for nonopioid interventions. Pharmacists worked closely with clinicians on safely tapering these medications in patients taking high doses.
The program worked, according to Dr. Goldzweig. Dr. Goldzweig could only find two patients currently taking high-dose opioids in the system’s database out of more than 7000 patients with Medicare Advantage insurance coverage.
“There will always be some patients who have no alternative than opioids, but we established some discipline with urine tox screens and pain agreements, and over time, we’ve been able to reduce the number of high-risk opioid prescriptions,” she said.
A version of this article first appeared on Medscape.com.
Prescribing Epilepsy Meds in Pregnancy: ‘We Can Do Better,’ Experts Say
HELSINKI, FINLAND — When it comes to caring for women with epilepsy who become pregnant, there is a great deal of room for improvement, experts say.
“Too many women with epilepsy receive information about epilepsy and pregnancy only after pregnancy. We can do better,” Torbjörn Tomson, MD, PhD, senior professor of neurology and epileptology, Karolinska Institutet, Stockholm, Sweden, told delegates attending the Congress of the European Academy of Neurology 2024.
The goal in epilepsy is to maintain seizure control while minimizing exposure to potentially teratogenic medications, Dr. Tomson said. He added that pregnancy planning in women with epilepsy is important but also conceded that most pregnancies in this patient population are unplanned.
Overall, it’s important to tell patients that “there is a high likelihood of an uneventful pregnancy and a healthy offspring,” he said.
In recent years, new data have emerged on the risks to the fetus with exposure to different antiseizure medications (ASMs), said Dr. Tomson. This has led regulators, such as the US Food and Drug Administration and the European Medicines Agency, to issue restrictions on the use of some ASMs, particularly valproate and topiramate, in females of childbearing age.
Session chair Marte Bjørk, MD, PhD, of the Department of Neurology of Haukeland University Hospital, Bergen, Norway, questioned whether the latest recommendations from regulatory authorities have “sacrificed seizure control at the expense of teratogenic safety.”
To an extent, this is true, said Dr. Tomson, “as the regulations prioritize fetal health over women’s health.” However, “we have not seen poorer seizure control with newer medications” in recent datasets.
It’s about good planning, said Dr. Bjork, who is responsible for the clinical guidelines for treatment of epilepsy in pregnancy in Norway.
Start With Folic Acid
One simple measure is to ensure that all women with epilepsy of childbearing age are prescribed low-dose folic acid, Dr. Tomson said — even those who report that they are not considering pregnancy.
When it comes to folic acid, recently published guidelines on ASM use during pregnancy are relatively straightforward, he said.
The data do not show that folic acid reduces the risk for major congenital malformations, but they do show that it improves neurocognitive outcomes in children of mothers who received folic acid supplements prior to and throughout pregnancy.
Dr. Tomson said the new American Academy of Neurology (AAN) guidelines recommend a dosage of 0.4 mg/d, which balances the demonstrated benefits of supplementation and potential negative consequences of high doses of folic acid.
“Consider 0.4 mg of folic acid for all women on ASMs that are of childbearing potential, whether they become pregnant or not,” he said. However, well-designed, preferably randomized, studies are needed to better define the optimal folic acid dosing for pregnancy in women with epilepsy.
Choosing the Right ASM
The choice of the most appropriate ASM in pregnancy is based on the potential for an individual drug to cause major congenital malformations and, in more recent years, the likelihood that a woman with epilepsy is using any other medications associated with neurodevelopmental disorders in offspring.
Balanced against this must be the effect of pregnancy on seizure control, and the maternal and fetal risks associated with seizures during pregnancy.
“There are ways to optimize seizure control and to reduce teratogenic risks,” said Dr. Tomson, adding that the new AAN guidelines provide updated evidence-based conclusions on this topic.
The good news is that “there has been almost a 40% decline in the rate of major congenital malformations associated with ASM use in pregnancy, in parallel with a shift from use of ASMs such as carbamazepine and valproate to lamotrigine and levetiracetam.” The latter two medications are associated with a much lower risk for such birth defects, he added.
This is based on the average rate of major congenital malformations in the EURAP registry that tracks the comparative risk for major fetal malformations after ASM use during pregnancy in over 40 countries. The latest reporting from the registry shows that this risk has decreased from 6.1% in 1998-2004 to 3.7% in 2015-2022.
Taking valproate during pregnancy is associated with a significantly increased risk for neurodevelopmental outcomes, including autism spectrum disorder. However, the jury is still out on whether topiramate escalates the risk for neurodevelopmental disorders, because findings across studies have been inconsistent.
Overall, the AAN guidance, and similar advice from European regulatory authorities, is that valproate is associated with high risk for major congenital malformations and neurodevelopmental disorders. Topiramate has also been shown to increase the risk for major congenital malformations. Consequently, these two anticonvulsants are generally contraindicated in pregnancy, Dr. Tomson noted.
On the other hand, levetiracetam, lamotrigine, and oxcarbazepine seem to be the safest ASMs with respect to congenital malformation risk, and lamotrigine has the best documented safety profile when it comes to the risk for neurodevelopmental disorders.
Although there are newer ASMs on the market, including brivaracetam, cannabidiol, cenobamate, eslicarbazepine acetate, fenfluramine, lacosamide, perampanel, and zonisamide, at this juncture data on the risk potential of these agents are insufficient.
“For some of these newer meds, we don’t even have a single exposure in our large databases, even if you combine them all. We need to collect more data, and that will take time,” Dr. Tomson said.
Dose Optimization
Dose optimization of ASMs is also important — and for this to be accurate, it’s important to document an individual’s optimal ASM serum levels before pregnancy that can be used as a baseline target during pregnancy. However, Dr. Tomson noted, this information is not always available.
He pointed out that, with many ASMs, there can be a significant decline in serum concentration levels during pregnancy, which can increase seizure risk.
To address the uncertainty surrounding this issue, Dr. Tomson recommended that physicians consider future pregnancy when prescribing ASMs to women of childbearing age. He also advised discussing contraception with these patients, even if they indicate they are not currently planning to conceive.
The data clearly show the importance of planning a pregnancy so that the most appropriate and safest medications are prescribed, he said.
Dr. Tomson reported receiving research support, on behalf of EURAP, from Accord, Angelini, Bial, EcuPharma, Eisai, GlaxoSmithKline, Glenmark, GW Pharma, Hazz, Sanofi, Teva, USB, Zentiva, and SF Group. He has received speakers’ honoraria from Angelini, Eisai, and UCB. Dr. Bjørk reports receiving speakers’ honoraria from Pfizer, Eisai, AbbVie, Best Practice, Lilly, Novartis, and Teva. She has received unrestricted educational grants from The Research Council of Norway, the Research Council of the Nordic Countries (NordForsk), and the Norwegian Epilepsy Association. She has received consulting honoraria from Novartis and is on the advisory board of Eisai, Lundbeck, Angelini Pharma, and Jazz Pharmaceuticals. Dr. Bjørk also received institutional grants from marked authorization holders of valproate.
A version of this article first appeared on Medscape.com.
HELSINKI, FINLAND — When it comes to caring for women with epilepsy who become pregnant, there is a great deal of room for improvement, experts say.
“Too many women with epilepsy receive information about epilepsy and pregnancy only after pregnancy. We can do better,” Torbjörn Tomson, MD, PhD, senior professor of neurology and epileptology, Karolinska Institutet, Stockholm, Sweden, told delegates attending the Congress of the European Academy of Neurology 2024.
The goal in epilepsy is to maintain seizure control while minimizing exposure to potentially teratogenic medications, Dr. Tomson said. He added that pregnancy planning in women with epilepsy is important but also conceded that most pregnancies in this patient population are unplanned.
Overall, it’s important to tell patients that “there is a high likelihood of an uneventful pregnancy and a healthy offspring,” he said.
In recent years, new data have emerged on the risks to the fetus with exposure to different antiseizure medications (ASMs), said Dr. Tomson. This has led regulators, such as the US Food and Drug Administration and the European Medicines Agency, to issue restrictions on the use of some ASMs, particularly valproate and topiramate, in females of childbearing age.
Session chair Marte Bjørk, MD, PhD, of the Department of Neurology of Haukeland University Hospital, Bergen, Norway, questioned whether the latest recommendations from regulatory authorities have “sacrificed seizure control at the expense of teratogenic safety.”
To an extent, this is true, said Dr. Tomson, “as the regulations prioritize fetal health over women’s health.” However, “we have not seen poorer seizure control with newer medications” in recent datasets.
It’s about good planning, said Dr. Bjork, who is responsible for the clinical guidelines for treatment of epilepsy in pregnancy in Norway.
Start With Folic Acid
One simple measure is to ensure that all women with epilepsy of childbearing age are prescribed low-dose folic acid, Dr. Tomson said — even those who report that they are not considering pregnancy.
When it comes to folic acid, recently published guidelines on ASM use during pregnancy are relatively straightforward, he said.
The data do not show that folic acid reduces the risk for major congenital malformations, but they do show that it improves neurocognitive outcomes in children of mothers who received folic acid supplements prior to and throughout pregnancy.
Dr. Tomson said the new American Academy of Neurology (AAN) guidelines recommend a dosage of 0.4 mg/d, which balances the demonstrated benefits of supplementation and potential negative consequences of high doses of folic acid.
“Consider 0.4 mg of folic acid for all women on ASMs that are of childbearing potential, whether they become pregnant or not,” he said. However, well-designed, preferably randomized, studies are needed to better define the optimal folic acid dosing for pregnancy in women with epilepsy.
Choosing the Right ASM
The choice of the most appropriate ASM in pregnancy is based on the potential for an individual drug to cause major congenital malformations and, in more recent years, the likelihood that a woman with epilepsy is using any other medications associated with neurodevelopmental disorders in offspring.
Balanced against this must be the effect of pregnancy on seizure control, and the maternal and fetal risks associated with seizures during pregnancy.
“There are ways to optimize seizure control and to reduce teratogenic risks,” said Dr. Tomson, adding that the new AAN guidelines provide updated evidence-based conclusions on this topic.
The good news is that “there has been almost a 40% decline in the rate of major congenital malformations associated with ASM use in pregnancy, in parallel with a shift from use of ASMs such as carbamazepine and valproate to lamotrigine and levetiracetam.” The latter two medications are associated with a much lower risk for such birth defects, he added.
This is based on the average rate of major congenital malformations in the EURAP registry that tracks the comparative risk for major fetal malformations after ASM use during pregnancy in over 40 countries. The latest reporting from the registry shows that this risk has decreased from 6.1% in 1998-2004 to 3.7% in 2015-2022.
Taking valproate during pregnancy is associated with a significantly increased risk for neurodevelopmental outcomes, including autism spectrum disorder. However, the jury is still out on whether topiramate escalates the risk for neurodevelopmental disorders, because findings across studies have been inconsistent.
Overall, the AAN guidance, and similar advice from European regulatory authorities, is that valproate is associated with high risk for major congenital malformations and neurodevelopmental disorders. Topiramate has also been shown to increase the risk for major congenital malformations. Consequently, these two anticonvulsants are generally contraindicated in pregnancy, Dr. Tomson noted.
On the other hand, levetiracetam, lamotrigine, and oxcarbazepine seem to be the safest ASMs with respect to congenital malformation risk, and lamotrigine has the best documented safety profile when it comes to the risk for neurodevelopmental disorders.
Although there are newer ASMs on the market, including brivaracetam, cannabidiol, cenobamate, eslicarbazepine acetate, fenfluramine, lacosamide, perampanel, and zonisamide, at this juncture data on the risk potential of these agents are insufficient.
“For some of these newer meds, we don’t even have a single exposure in our large databases, even if you combine them all. We need to collect more data, and that will take time,” Dr. Tomson said.
Dose Optimization
Dose optimization of ASMs is also important — and for this to be accurate, it’s important to document an individual’s optimal ASM serum levels before pregnancy that can be used as a baseline target during pregnancy. However, Dr. Tomson noted, this information is not always available.
He pointed out that, with many ASMs, there can be a significant decline in serum concentration levels during pregnancy, which can increase seizure risk.
To address the uncertainty surrounding this issue, Dr. Tomson recommended that physicians consider future pregnancy when prescribing ASMs to women of childbearing age. He also advised discussing contraception with these patients, even if they indicate they are not currently planning to conceive.
The data clearly show the importance of planning a pregnancy so that the most appropriate and safest medications are prescribed, he said.
Dr. Tomson reported receiving research support, on behalf of EURAP, from Accord, Angelini, Bial, EcuPharma, Eisai, GlaxoSmithKline, Glenmark, GW Pharma, Hazz, Sanofi, Teva, USB, Zentiva, and SF Group. He has received speakers’ honoraria from Angelini, Eisai, and UCB. Dr. Bjørk reports receiving speakers’ honoraria from Pfizer, Eisai, AbbVie, Best Practice, Lilly, Novartis, and Teva. She has received unrestricted educational grants from The Research Council of Norway, the Research Council of the Nordic Countries (NordForsk), and the Norwegian Epilepsy Association. She has received consulting honoraria from Novartis and is on the advisory board of Eisai, Lundbeck, Angelini Pharma, and Jazz Pharmaceuticals. Dr. Bjørk also received institutional grants from marked authorization holders of valproate.
A version of this article first appeared on Medscape.com.
HELSINKI, FINLAND — When it comes to caring for women with epilepsy who become pregnant, there is a great deal of room for improvement, experts say.
“Too many women with epilepsy receive information about epilepsy and pregnancy only after pregnancy. We can do better,” Torbjörn Tomson, MD, PhD, senior professor of neurology and epileptology, Karolinska Institutet, Stockholm, Sweden, told delegates attending the Congress of the European Academy of Neurology 2024.
The goal in epilepsy is to maintain seizure control while minimizing exposure to potentially teratogenic medications, Dr. Tomson said. He added that pregnancy planning in women with epilepsy is important but also conceded that most pregnancies in this patient population are unplanned.
Overall, it’s important to tell patients that “there is a high likelihood of an uneventful pregnancy and a healthy offspring,” he said.
In recent years, new data have emerged on the risks to the fetus with exposure to different antiseizure medications (ASMs), said Dr. Tomson. This has led regulators, such as the US Food and Drug Administration and the European Medicines Agency, to issue restrictions on the use of some ASMs, particularly valproate and topiramate, in females of childbearing age.
Session chair Marte Bjørk, MD, PhD, of the Department of Neurology of Haukeland University Hospital, Bergen, Norway, questioned whether the latest recommendations from regulatory authorities have “sacrificed seizure control at the expense of teratogenic safety.”
To an extent, this is true, said Dr. Tomson, “as the regulations prioritize fetal health over women’s health.” However, “we have not seen poorer seizure control with newer medications” in recent datasets.
It’s about good planning, said Dr. Bjork, who is responsible for the clinical guidelines for treatment of epilepsy in pregnancy in Norway.
Start With Folic Acid
One simple measure is to ensure that all women with epilepsy of childbearing age are prescribed low-dose folic acid, Dr. Tomson said — even those who report that they are not considering pregnancy.
When it comes to folic acid, recently published guidelines on ASM use during pregnancy are relatively straightforward, he said.
The data do not show that folic acid reduces the risk for major congenital malformations, but they do show that it improves neurocognitive outcomes in children of mothers who received folic acid supplements prior to and throughout pregnancy.
Dr. Tomson said the new American Academy of Neurology (AAN) guidelines recommend a dosage of 0.4 mg/d, which balances the demonstrated benefits of supplementation and potential negative consequences of high doses of folic acid.
“Consider 0.4 mg of folic acid for all women on ASMs that are of childbearing potential, whether they become pregnant or not,” he said. However, well-designed, preferably randomized, studies are needed to better define the optimal folic acid dosing for pregnancy in women with epilepsy.
Choosing the Right ASM
The choice of the most appropriate ASM in pregnancy is based on the potential for an individual drug to cause major congenital malformations and, in more recent years, the likelihood that a woman with epilepsy is using any other medications associated with neurodevelopmental disorders in offspring.
Balanced against this must be the effect of pregnancy on seizure control, and the maternal and fetal risks associated with seizures during pregnancy.
“There are ways to optimize seizure control and to reduce teratogenic risks,” said Dr. Tomson, adding that the new AAN guidelines provide updated evidence-based conclusions on this topic.
The good news is that “there has been almost a 40% decline in the rate of major congenital malformations associated with ASM use in pregnancy, in parallel with a shift from use of ASMs such as carbamazepine and valproate to lamotrigine and levetiracetam.” The latter two medications are associated with a much lower risk for such birth defects, he added.
This is based on the average rate of major congenital malformations in the EURAP registry that tracks the comparative risk for major fetal malformations after ASM use during pregnancy in over 40 countries. The latest reporting from the registry shows that this risk has decreased from 6.1% in 1998-2004 to 3.7% in 2015-2022.
Taking valproate during pregnancy is associated with a significantly increased risk for neurodevelopmental outcomes, including autism spectrum disorder. However, the jury is still out on whether topiramate escalates the risk for neurodevelopmental disorders, because findings across studies have been inconsistent.
Overall, the AAN guidance, and similar advice from European regulatory authorities, is that valproate is associated with high risk for major congenital malformations and neurodevelopmental disorders. Topiramate has also been shown to increase the risk for major congenital malformations. Consequently, these two anticonvulsants are generally contraindicated in pregnancy, Dr. Tomson noted.
On the other hand, levetiracetam, lamotrigine, and oxcarbazepine seem to be the safest ASMs with respect to congenital malformation risk, and lamotrigine has the best documented safety profile when it comes to the risk for neurodevelopmental disorders.
Although there are newer ASMs on the market, including brivaracetam, cannabidiol, cenobamate, eslicarbazepine acetate, fenfluramine, lacosamide, perampanel, and zonisamide, at this juncture data on the risk potential of these agents are insufficient.
“For some of these newer meds, we don’t even have a single exposure in our large databases, even if you combine them all. We need to collect more data, and that will take time,” Dr. Tomson said.
Dose Optimization
Dose optimization of ASMs is also important — and for this to be accurate, it’s important to document an individual’s optimal ASM serum levels before pregnancy that can be used as a baseline target during pregnancy. However, Dr. Tomson noted, this information is not always available.
He pointed out that, with many ASMs, there can be a significant decline in serum concentration levels during pregnancy, which can increase seizure risk.
To address the uncertainty surrounding this issue, Dr. Tomson recommended that physicians consider future pregnancy when prescribing ASMs to women of childbearing age. He also advised discussing contraception with these patients, even if they indicate they are not currently planning to conceive.
The data clearly show the importance of planning a pregnancy so that the most appropriate and safest medications are prescribed, he said.
Dr. Tomson reported receiving research support, on behalf of EURAP, from Accord, Angelini, Bial, EcuPharma, Eisai, GlaxoSmithKline, Glenmark, GW Pharma, Hazz, Sanofi, Teva, USB, Zentiva, and SF Group. He has received speakers’ honoraria from Angelini, Eisai, and UCB. Dr. Bjørk reports receiving speakers’ honoraria from Pfizer, Eisai, AbbVie, Best Practice, Lilly, Novartis, and Teva. She has received unrestricted educational grants from The Research Council of Norway, the Research Council of the Nordic Countries (NordForsk), and the Norwegian Epilepsy Association. She has received consulting honoraria from Novartis and is on the advisory board of Eisai, Lundbeck, Angelini Pharma, and Jazz Pharmaceuticals. Dr. Bjørk also received institutional grants from marked authorization holders of valproate.
A version of this article first appeared on Medscape.com.
FROM EAN 2024
Buprenorphine One of Many Options For Pain Relief In Oldest Adults
Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.
These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.
“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.
Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.
“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.
Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.
The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.
“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.
Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
Nonpharmacologic Remedies, Drug Considerations
“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.
Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.
Sometimes medication is necessary, however.
“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.
When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.
“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.
Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.
“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.
Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.
Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.
When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.
Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.
This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.
“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”
Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.
“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.
Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.
These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.
“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.
Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.
“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.
Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.
The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.
“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.
Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
Nonpharmacologic Remedies, Drug Considerations
“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.
Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.
Sometimes medication is necessary, however.
“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.
When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.
“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.
Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.
“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.
Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.
Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.
When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.
Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.
This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.
“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”
Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.
“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.
Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.
These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.
“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.
Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.
“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.
Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.
The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.
“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.
Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
Nonpharmacologic Remedies, Drug Considerations
“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.
Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.
Sometimes medication is necessary, however.
“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.
When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.
“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.
Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.
“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.
Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.
Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.
When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.
Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.
This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.
“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”
Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.
“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.
Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
Night Owl or Lark? The Answer May Affect Cognition
new research suggests.
“Rather than just being personal preferences, these chronotypes could impact our cognitive function,” said study investigator, Raha West, MBChB, with Imperial College London, London, England, in a statement.
But the researchers also urged caution when interpreting the findings.
“It’s important to note that this doesn’t mean all morning people have worse cognitive performance. The findings reflect an overall trend where the majority might lean toward better cognition in the evening types,” Dr. West added.
In addition, across the board, getting the recommended 7-9 hours of nightly sleep was best for cognitive function, and sleeping for less than 7 or more than 9 hours had detrimental effects on brain function regardless of whether an individual was a night owl or lark.
The study was published online in BMJ Public Health.
A UK Biobank Cohort Study
The findings are based on a cross-sectional analysis of 26,820 adults aged 53-86 years from the UK Biobank database, who were categorized into two cohorts.
Cohort 1 had 10,067 participants (56% women) who completed four cognitive tests measuring fluid intelligence/reasoning, pairs matching, reaction time, and prospective memory. Cohort 2 had 16,753 participants (56% women) who completed two cognitive assessments (pairs matching and reaction time).
Participants self-reported sleep duration, chronotype, and quality. Cognitive test scores were evaluated against sleep parameters and health and lifestyle factors including sex, age, vascular and cardiac conditions, diabetes,alcohol use, smoking habits, and body mass index.
The results revealed a positive association between normal sleep duration (7-9 hours) and cognitive scores in Cohort 1 (beta, 0.0567), while extended sleep duration negatively impacted scores across in Cohort 1 and 2 (beta, –0.188 and beta, –0.2619, respectively).
An individual’s preference for evening or morning activity correlated strongly with their test scores. In particular, night owls consistently performed better on cognitive tests than early birds.
“While understanding and working with your natural sleep tendencies is essential, it’s equally important to remember to get just enough sleep, not too long or too short,” Dr. West noted. “This is crucial for keeping your brain healthy and functioning at its best.”
Contrary to some previous findings, the study did not find a significant relationship between sleep, sleepiness/insomnia, and cognitive performance. This may be because specific aspects of insomnia, such as severity and chronicity, as well as comorbid conditions need to be considered, the investigators wrote.
They added that age and diabetes consistently emerged as negative predictors of cognitive functioning across both cohorts, in line with previous research.
Limitations of the study include the cross-sectional design, which limits causal inferences; the possibility of residual confounding; and reliance on self-reported sleep data.
Also, the study did not adjust for educational attainment, a factor potentially influential on cognitive performance and sleep patterns, because of incomplete data. The study also did not factor in depression and social isolation, which have been shown to increase the risk for cognitive decline.
No Real-World Implications
Several outside experts offered their perspective on the study in a statement from the UK nonprofit Science Media Centre.
The study provides “interesting insights” into the difference in memory and thinking in people who identify themselves as a “morning” or “evening” person, Jacqui Hanley, PhD, with Alzheimer’s Research UK, said in the statement.
However, without a detailed picture of what is going on in the brain, it’s not clear whether being a morning or evening person affects memory and thinking or whether a decline in cognition is causing changes to sleeping patterns, Dr. Hanley added.
Roi Cohen Kadosh, PhD, CPsychol, professor of cognitive neuroscience, University of Surrey, Guildford, England, cautioned that there are “multiple potential reasons” for these associations.
“Therefore, there are no implications in my view for the real world. I fear that the general public will not be able to understand that and will change their sleep pattern, while this study does not give any evidence that this will lead to any benefit,” Dr. Cohen Kadosh said.
Jessica Chelekis, PhD, MBA, a sleep expert from Brunel University London, Uxbridge, England, said that the “main takeaway should be that the cultural belief that early risers are more productive than ‘night owls’ does not hold up to scientific scrutiny.”
“While everyone should aim to get good-quality sleep each night, we should also try to be aware of what time of day we are at our (cognitive) best and work in ways that suit us. Night owls, in particular, should not be shamed into fitting a stereotype that favors an ‘early to bed, early to rise’ practice,” Dr. Chelekis said.
Funding for the study was provided by the Korea Institute of Oriental Medicine in collaboration with Imperial College London. Dr. Hanley, Dr. Cohen Kadosh, and Dr. Chelekis have no relevant disclosures.
A version of this article first appeared on Medscape.com.
new research suggests.
“Rather than just being personal preferences, these chronotypes could impact our cognitive function,” said study investigator, Raha West, MBChB, with Imperial College London, London, England, in a statement.
But the researchers also urged caution when interpreting the findings.
“It’s important to note that this doesn’t mean all morning people have worse cognitive performance. The findings reflect an overall trend where the majority might lean toward better cognition in the evening types,” Dr. West added.
In addition, across the board, getting the recommended 7-9 hours of nightly sleep was best for cognitive function, and sleeping for less than 7 or more than 9 hours had detrimental effects on brain function regardless of whether an individual was a night owl or lark.
The study was published online in BMJ Public Health.
A UK Biobank Cohort Study
The findings are based on a cross-sectional analysis of 26,820 adults aged 53-86 years from the UK Biobank database, who were categorized into two cohorts.
Cohort 1 had 10,067 participants (56% women) who completed four cognitive tests measuring fluid intelligence/reasoning, pairs matching, reaction time, and prospective memory. Cohort 2 had 16,753 participants (56% women) who completed two cognitive assessments (pairs matching and reaction time).
Participants self-reported sleep duration, chronotype, and quality. Cognitive test scores were evaluated against sleep parameters and health and lifestyle factors including sex, age, vascular and cardiac conditions, diabetes,alcohol use, smoking habits, and body mass index.
The results revealed a positive association between normal sleep duration (7-9 hours) and cognitive scores in Cohort 1 (beta, 0.0567), while extended sleep duration negatively impacted scores across in Cohort 1 and 2 (beta, –0.188 and beta, –0.2619, respectively).
An individual’s preference for evening or morning activity correlated strongly with their test scores. In particular, night owls consistently performed better on cognitive tests than early birds.
“While understanding and working with your natural sleep tendencies is essential, it’s equally important to remember to get just enough sleep, not too long or too short,” Dr. West noted. “This is crucial for keeping your brain healthy and functioning at its best.”
Contrary to some previous findings, the study did not find a significant relationship between sleep, sleepiness/insomnia, and cognitive performance. This may be because specific aspects of insomnia, such as severity and chronicity, as well as comorbid conditions need to be considered, the investigators wrote.
They added that age and diabetes consistently emerged as negative predictors of cognitive functioning across both cohorts, in line with previous research.
Limitations of the study include the cross-sectional design, which limits causal inferences; the possibility of residual confounding; and reliance on self-reported sleep data.
Also, the study did not adjust for educational attainment, a factor potentially influential on cognitive performance and sleep patterns, because of incomplete data. The study also did not factor in depression and social isolation, which have been shown to increase the risk for cognitive decline.
No Real-World Implications
Several outside experts offered their perspective on the study in a statement from the UK nonprofit Science Media Centre.
The study provides “interesting insights” into the difference in memory and thinking in people who identify themselves as a “morning” or “evening” person, Jacqui Hanley, PhD, with Alzheimer’s Research UK, said in the statement.
However, without a detailed picture of what is going on in the brain, it’s not clear whether being a morning or evening person affects memory and thinking or whether a decline in cognition is causing changes to sleeping patterns, Dr. Hanley added.
Roi Cohen Kadosh, PhD, CPsychol, professor of cognitive neuroscience, University of Surrey, Guildford, England, cautioned that there are “multiple potential reasons” for these associations.
“Therefore, there are no implications in my view for the real world. I fear that the general public will not be able to understand that and will change their sleep pattern, while this study does not give any evidence that this will lead to any benefit,” Dr. Cohen Kadosh said.
Jessica Chelekis, PhD, MBA, a sleep expert from Brunel University London, Uxbridge, England, said that the “main takeaway should be that the cultural belief that early risers are more productive than ‘night owls’ does not hold up to scientific scrutiny.”
“While everyone should aim to get good-quality sleep each night, we should also try to be aware of what time of day we are at our (cognitive) best and work in ways that suit us. Night owls, in particular, should not be shamed into fitting a stereotype that favors an ‘early to bed, early to rise’ practice,” Dr. Chelekis said.
Funding for the study was provided by the Korea Institute of Oriental Medicine in collaboration with Imperial College London. Dr. Hanley, Dr. Cohen Kadosh, and Dr. Chelekis have no relevant disclosures.
A version of this article first appeared on Medscape.com.
new research suggests.
“Rather than just being personal preferences, these chronotypes could impact our cognitive function,” said study investigator, Raha West, MBChB, with Imperial College London, London, England, in a statement.
But the researchers also urged caution when interpreting the findings.
“It’s important to note that this doesn’t mean all morning people have worse cognitive performance. The findings reflect an overall trend where the majority might lean toward better cognition in the evening types,” Dr. West added.
In addition, across the board, getting the recommended 7-9 hours of nightly sleep was best for cognitive function, and sleeping for less than 7 or more than 9 hours had detrimental effects on brain function regardless of whether an individual was a night owl or lark.
The study was published online in BMJ Public Health.
A UK Biobank Cohort Study
The findings are based on a cross-sectional analysis of 26,820 adults aged 53-86 years from the UK Biobank database, who were categorized into two cohorts.
Cohort 1 had 10,067 participants (56% women) who completed four cognitive tests measuring fluid intelligence/reasoning, pairs matching, reaction time, and prospective memory. Cohort 2 had 16,753 participants (56% women) who completed two cognitive assessments (pairs matching and reaction time).
Participants self-reported sleep duration, chronotype, and quality. Cognitive test scores were evaluated against sleep parameters and health and lifestyle factors including sex, age, vascular and cardiac conditions, diabetes,alcohol use, smoking habits, and body mass index.
The results revealed a positive association between normal sleep duration (7-9 hours) and cognitive scores in Cohort 1 (beta, 0.0567), while extended sleep duration negatively impacted scores across in Cohort 1 and 2 (beta, –0.188 and beta, –0.2619, respectively).
An individual’s preference for evening or morning activity correlated strongly with their test scores. In particular, night owls consistently performed better on cognitive tests than early birds.
“While understanding and working with your natural sleep tendencies is essential, it’s equally important to remember to get just enough sleep, not too long or too short,” Dr. West noted. “This is crucial for keeping your brain healthy and functioning at its best.”
Contrary to some previous findings, the study did not find a significant relationship between sleep, sleepiness/insomnia, and cognitive performance. This may be because specific aspects of insomnia, such as severity and chronicity, as well as comorbid conditions need to be considered, the investigators wrote.
They added that age and diabetes consistently emerged as negative predictors of cognitive functioning across both cohorts, in line with previous research.
Limitations of the study include the cross-sectional design, which limits causal inferences; the possibility of residual confounding; and reliance on self-reported sleep data.
Also, the study did not adjust for educational attainment, a factor potentially influential on cognitive performance and sleep patterns, because of incomplete data. The study also did not factor in depression and social isolation, which have been shown to increase the risk for cognitive decline.
No Real-World Implications
Several outside experts offered their perspective on the study in a statement from the UK nonprofit Science Media Centre.
The study provides “interesting insights” into the difference in memory and thinking in people who identify themselves as a “morning” or “evening” person, Jacqui Hanley, PhD, with Alzheimer’s Research UK, said in the statement.
However, without a detailed picture of what is going on in the brain, it’s not clear whether being a morning or evening person affects memory and thinking or whether a decline in cognition is causing changes to sleeping patterns, Dr. Hanley added.
Roi Cohen Kadosh, PhD, CPsychol, professor of cognitive neuroscience, University of Surrey, Guildford, England, cautioned that there are “multiple potential reasons” for these associations.
“Therefore, there are no implications in my view for the real world. I fear that the general public will not be able to understand that and will change their sleep pattern, while this study does not give any evidence that this will lead to any benefit,” Dr. Cohen Kadosh said.
Jessica Chelekis, PhD, MBA, a sleep expert from Brunel University London, Uxbridge, England, said that the “main takeaway should be that the cultural belief that early risers are more productive than ‘night owls’ does not hold up to scientific scrutiny.”
“While everyone should aim to get good-quality sleep each night, we should also try to be aware of what time of day we are at our (cognitive) best and work in ways that suit us. Night owls, in particular, should not be shamed into fitting a stereotype that favors an ‘early to bed, early to rise’ practice,” Dr. Chelekis said.
Funding for the study was provided by the Korea Institute of Oriental Medicine in collaboration with Imperial College London. Dr. Hanley, Dr. Cohen Kadosh, and Dr. Chelekis have no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM BMJ PUBLIC HEALTH
EMA Warns of Anaphylactic Reactions to MS Drug
Such reactions could occur even years after the start of treatment, the European Medicines Agency (EMA) warned.
Glatiramer acetate is a disease-modifying therapy (DMT) for relapsing MS that is given by injection.
The drug has been used for treating MS for more than 20 years, during which time, it has had a good safety profile. Common side effects are known to include vasodilation, arthralgia, anxiety, hypertonia, palpitations, and lipoatrophy.
A meeting of the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), held on July 8-11, considered evidence from an EU-wide review of all available data concerning anaphylactic reactions with glatiramer acetate. As a result, the committee concluded that the medicine is associated with a risk for anaphylactic reactions, which may occur shortly after administration or even months or years later.
Risk for Delays to Treatment
Cases involving the use of glatiramer acetate with a fatal outcome have been reported, PRAC noted.
The committee cautioned that because the initial symptoms could overlap with those of postinjection reaction, there was a risk for delay in identifying an anaphylactic reaction.
PRAC has sanctioned a direct healthcare professional communication (DHPC) to inform healthcare professionals about the risk. Patients and caregivers should be advised of the signs and symptoms of an anaphylactic reaction and the need to seek emergency care if this should occur, the committee added. In the event of such a reaction, treatment with glatiramer acetate must be discontinued, PRAC stated.
Once adopted, the DHPC for glatiramer acetate will be disseminated to healthcare professionals by the marketing authorization holders.
Anaphylactic reactions associated with the use of glatiramer acetate have been noted in medical literature for some years. A letter by members of the department of neurology at Albert Ludwig University Freiburg, Freiburg im Bresigau, Germany, published in the journal European Neurology in 2011, detailed six cases of anaphylactoid or anaphylactic reactions in patients while they were undergoing treatment with glatiramer acetate.
The authors highlighted that in one of the cases, a grade 1 anaphylactic reaction occurred 3 months after treatment with the drug was initiated.
A version of this article first appeared on Medscape.com.
Such reactions could occur even years after the start of treatment, the European Medicines Agency (EMA) warned.
Glatiramer acetate is a disease-modifying therapy (DMT) for relapsing MS that is given by injection.
The drug has been used for treating MS for more than 20 years, during which time, it has had a good safety profile. Common side effects are known to include vasodilation, arthralgia, anxiety, hypertonia, palpitations, and lipoatrophy.
A meeting of the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), held on July 8-11, considered evidence from an EU-wide review of all available data concerning anaphylactic reactions with glatiramer acetate. As a result, the committee concluded that the medicine is associated with a risk for anaphylactic reactions, which may occur shortly after administration or even months or years later.
Risk for Delays to Treatment
Cases involving the use of glatiramer acetate with a fatal outcome have been reported, PRAC noted.
The committee cautioned that because the initial symptoms could overlap with those of postinjection reaction, there was a risk for delay in identifying an anaphylactic reaction.
PRAC has sanctioned a direct healthcare professional communication (DHPC) to inform healthcare professionals about the risk. Patients and caregivers should be advised of the signs and symptoms of an anaphylactic reaction and the need to seek emergency care if this should occur, the committee added. In the event of such a reaction, treatment with glatiramer acetate must be discontinued, PRAC stated.
Once adopted, the DHPC for glatiramer acetate will be disseminated to healthcare professionals by the marketing authorization holders.
Anaphylactic reactions associated with the use of glatiramer acetate have been noted in medical literature for some years. A letter by members of the department of neurology at Albert Ludwig University Freiburg, Freiburg im Bresigau, Germany, published in the journal European Neurology in 2011, detailed six cases of anaphylactoid or anaphylactic reactions in patients while they were undergoing treatment with glatiramer acetate.
The authors highlighted that in one of the cases, a grade 1 anaphylactic reaction occurred 3 months after treatment with the drug was initiated.
A version of this article first appeared on Medscape.com.
Such reactions could occur even years after the start of treatment, the European Medicines Agency (EMA) warned.
Glatiramer acetate is a disease-modifying therapy (DMT) for relapsing MS that is given by injection.
The drug has been used for treating MS for more than 20 years, during which time, it has had a good safety profile. Common side effects are known to include vasodilation, arthralgia, anxiety, hypertonia, palpitations, and lipoatrophy.
A meeting of the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), held on July 8-11, considered evidence from an EU-wide review of all available data concerning anaphylactic reactions with glatiramer acetate. As a result, the committee concluded that the medicine is associated with a risk for anaphylactic reactions, which may occur shortly after administration or even months or years later.
Risk for Delays to Treatment
Cases involving the use of glatiramer acetate with a fatal outcome have been reported, PRAC noted.
The committee cautioned that because the initial symptoms could overlap with those of postinjection reaction, there was a risk for delay in identifying an anaphylactic reaction.
PRAC has sanctioned a direct healthcare professional communication (DHPC) to inform healthcare professionals about the risk. Patients and caregivers should be advised of the signs and symptoms of an anaphylactic reaction and the need to seek emergency care if this should occur, the committee added. In the event of such a reaction, treatment with glatiramer acetate must be discontinued, PRAC stated.
Once adopted, the DHPC for glatiramer acetate will be disseminated to healthcare professionals by the marketing authorization holders.
Anaphylactic reactions associated with the use of glatiramer acetate have been noted in medical literature for some years. A letter by members of the department of neurology at Albert Ludwig University Freiburg, Freiburg im Bresigau, Germany, published in the journal European Neurology in 2011, detailed six cases of anaphylactoid or anaphylactic reactions in patients while they were undergoing treatment with glatiramer acetate.
The authors highlighted that in one of the cases, a grade 1 anaphylactic reaction occurred 3 months after treatment with the drug was initiated.
A version of this article first appeared on Medscape.com.