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How PCPs Can Contribute to Epilepsy Care
The Centers for Disease Control and Prevention (CDC) estimates that 1.1% of US adults have epilepsy. Although 89% report seeing a physician in the past year about their condition, only 62% of adults saw a neurologist or seizure specialist.
These findings prompted Rosemary Kobau, MPH, the acting team lead for the CDC’s epilepsy program, to take a closer look at referral patterns by primary care providers in the United States.
She also noticed what she calls a “big red flag”: “We found that 40% of primary care providers did not indicate that they would refer their patient with epilepsy to a neurologist when their patient fails to respond to treatment, or if they have a change in seizure activity,” Dr. Kobau told this news organization. Individuals with uncontrolled seizures are at risk for multiple adverse health outcomes, along with emotional problems, social stigma, and decreased life expectancy.
Factors that influenced primary care clinicians to refer to a neurologist included prompt availability of appointments, ability to talk to the neurologist, and whether a patient’s insurance covered specialty visits. Proximity of a specialist also was cited as a barrier, because neurologists can be hard to find outside of urban centers.
Wait lists for neurologist are not like to get shorter any time soon, according to a 2019 report from the American Academy of Neurology (AAN). A 2013 workforce report from the AAN found 35 US states, representing 62% of the US population, had fewer neurologists than needed to meet demand. By 2025, demand is projected to exceed supply in 41 states.
Much of the increasing demand for adult neurologists is driven by aging of the population, resulting in higher rates of stroke, Parkinson’s disease, and dementia. But pediatric neurologists are also overwhelmed: Pediatric neurology is one of the top three pediatric subspecialties with the longest wait times. The shortage is exacerbated by difficulties in transitioning adolescents with epilepsy — many diagnosed early in life with neurodevelopmental and epileptic encephalopathy and problem lists that include learning disorders, behavioral issues, and other chronic medical problems — to adult epilepsy specialists.
Although one of the solutions offered by the AAN is more training in epilepsy management for non-neurologists (such as CME programs developed by the American Epilepsy Society), many primary care providers are overwhelmed already. Still, primary care providers are well-positioned to help answer some of the most important questions about the management of patients with seizure disorders.
How to Help
“There’s a lot the pediatrician can do when a child presents with seizures,” said Sucheta Joshi, MD, who serves as the medical director of the Neurological Institute Comprehensive Epilepsy Center at Children’s Hospital Los Angeles.
Step one is helping to allay the fears of family members who witness a seizure. “They can talk about seizure safety, they can talk about first aid when a seizure happens, they can talk about what to do, what not to do,” she advised. Clinicians who see children can find resources for families on the American Academy of Pediatrics (AAP) National Coordinating Center for Epilepsy website, including a 24/7 helpline, information about local chapters of the Epilepsy Foundation, and first aid training for seizures.
Fred Lado, MD, PhD, a professor of neurology at the Zucker School of Medicine at Hofstra-Norwell in Hempstead, New York, said that primary care clinicians have several decision points when it comes to their patients with epilepsy.
The first is whether to initiate medication after the first episode of seizure. Studies show that the risk for a second seizure decreases in patients started on anticonvulsant therapy after a first event, but many clinicians don›t want to commit patients to long-term therapy without more evidence that the patient has epilepsy. Studies have shown that delaying therapy until a second seizure occurs doesn›t negatively affect quality of life and long-term prognosis.
The International League Against Epilepsy (ILAE) advised treatment for patients with two or more unprovoked seizures but revised its recommendation in 2014 to begin treatment after a first seizure for individuals at high risk for a second seizure. History of a brain insult related to a stroke, mass lesion in the brain, or trauma are risk factors for a second seizure, whereas seizures provoked by a concussion, alcohol withdrawal, or exposure to toxins carry low risk for additional episodes.
Dr. Lado also raised the importance of taking a good history from a patient presenting for medical care for a new-onset seizure to determine whether the recent episode is really the first such incident.
Up to half of patients presenting to emergency departments for convulsive seizures have a history of a preceding nonmotor seizure that the patient or their family members have failed to identify. As many as 60% of people with epilepsy have focal seizures, but the majority of these are nonmotor seizures. As a result, these patients often go without a diagnosis until they develop bilateral tonic-clonic seizures — by which time they may already been injured during a seizure or had an accident while driving.
In terms of imaging and other workup that should be performed prior to the first appointment with a pediatric neurologist or epilepsy specialist, Dr. Joshi generally recommends EEG. She also prefers MRI over CT, which is better for finding lesions that tend to cause seizures in kids such as developmental abnormalities like a cortical malformation or a perinatal process. Obtaining an MRI prior to seeing the neurologist is elective, depending on whether the history and clinical presentation suggest a focal lesion.
For adults, Dr. Lado also recommends an EEG and MRI to start but rarely advises other laboratory studies. When patients present to the emergency department with a new-onset seizure, the workup commonly includes a chemistry panel to rule out hypoglycemia or electrolyte abnormalities. But in the outpatient setting, where a patient describes symptoms of a seizure that occurred a week ago or longer, Dr. Lado said the yield of such assessments is low.
“I think the labs are often more useful as you’re thinking about an anticonvulsant,” Dr. Lado said. Particularly for a patient who is facing a long wait to see specialist, obtaining baseline liver enzymes and a complete blood cell count is worthwhile, because many antiseizure medications can cause anemia or liver damage.
Dr. Lado agreed that referral to a specialist is critical for patients with drug-resistant seizures, defined by the ILAE as seizures that persist despite the use of two or more anticonvulsants.
“One of the great problems in epilepsy care is a sort of sense of complacency,” he said. Some of his own patients have become comfortable with their epilepsy diagnosis and profess to be untroubled by having a few seizures per year. In 2018, Dr. Kobau was a co-author on a study reporting that less than half of US adults taking seizure medications were seizure-free in the past year.
This scenario is an opportunity for primary care providers to help determine whether their patients are taking their antiseizure medication correctly. A referral to a specialist might not be necessary if the seizures are occurring because the patient’s prescription ran out. Similarly, if a patient doesn’t take the medication because of unpleasant side effects, raising the dose won’t help.
Dr. Lado’s advice is to explore why the patient’s management plan is not working and make adjustments tailored to their needs. The solution might be as simple as changing the patient to an extended-release formulation to lower the number of daily doses needed, he said.
But for patients who do have recurrent seizures despite good adherence, Dr. Lado strongly urges a referral to an epilepsy specialist. He serves as president of the National Association of Epilepsy Centers (NAEC), a network of more than 260 epilepsy centers in the United States that offer the services of epileptologists, neurosurgeons, neuropsychologists, nurse specialists, EEG technologists, social workers, and others with training and experience in epilepsy care. In addition to adjusting and monitoring medications, patients seen at an NAEC can be evaluated for surgery, neurostimulators, and ketogenic diets.
Improving Self-Management
Another role that primary care can play is promoting self-efficacy among patients with epilepsy.
“Providers have historically tended to focus on medication adherence alone, ignoring other health enhancing behaviors, even just sleep hygiene,” Dr. Kobau said. But adequate sleep, regular exercise, a healthy diet, avoidance of tobacco and excessive alcohol, and stress management are all important for seizure management.
In 2007, CDC launched the Managing Epilepsy Well (MEW) Network, which has the mission of advancing self-management research in collaboration with patients with epilepsy as well as a broad range of healthcare providers. “It’s a patient-driven kind of approach consistent with community-based, participatory practice research,” said Dr. Kobau, who oversees the initiative.
The MEW network, which consists of six prevention research centers funded by CDC, has piloted and evaluated several evidence-based programs that can help patients better control their epilepsy.
One such intervention is Project Uplift, which delivers mindfulness-based cognitive-behavioral therapy in a virtual group setting. Behavioral therapy is important for people with seizure disorders, whose risk for depression is more than twice that of the general population. The initial trial found the intervention was effective in reducing depressive symptoms in participants, and research since has focused on adapting the program to provide culturally appropriate care to underserved populations. The eight sessions, held weekly, are available in both English and Spanish.
Another program, HOBSCOTCH, allows patients to meet one-on-one virtually with a trained coach to work on skills for improving attention and memory, common problems among people with epilepsy.
MINDSET involves a tablet-based clinical decision tool that patients can use to track their self-management behaviors, such as taking their medications, seizure triggers, symptoms of depression, and keeping their clinic appointments. It also helps them monitor whether they are getting adequate sleep, reducing their stress, and maintaining social networks. The tool generates a printable action plan for patients to prompt discussion and shared decision-making between patient and clinician to prioritize behavioral issues, set goals, and monitor changes over time.
Clinicians can refer patients to any of the MEW interventions, or patients can enroll themselves online.
Emerging Approaches
The AAN’s 2019 report promoted use of technological solutions to bridge the gap between primary care providers and scarce — as well as distant — neurologists. Many health systems support e-consults between clinicians, allowing simple discussions about medications and advice about testing recommended prior to a neurology visit. Initially developed for treatment for infection with hepatitis C virus, Project Extension for Community Healthcare Outcomes (ECHO) uses a central hub of specialists to support primary care providers via teleconference to conduct case reviews and didactic sessions.
Much of Dr. Joshi’s work has focused on ways to coordinate care to children who live far from a pediatric epilepsy center. In a previous position at the University of Michigan, her team was one of four sites funded by the AAP’s National Coordinating Center for Epilepsy to pilot an intervention using telehealth. Implemented in 2017-2019, the initiative used quality improvement methodology to explore a model where patients went to the office of their primary care provider so that both could participate in the call with a neurologist.
The strategy was successful, resulting in reduced out-of-pocket costs, missed school hours, and missed work hours. Patient satisfaction was high (97%), and more parents in the intervention group than the control group agreed that it was easier to obtain appointments with specialists (95% vs 65%, respectively).
And since the pandemic, in-home telehealth visits have become commonplace, adding to the potential convenience and cost savings of telemedicine.
CDC has invested in Project ECHO as a training program for nonspecialist providers to manage epilepsy. Based at the University of Cincinnati, the initial pilot from 2017 to 2019 trained primary care providers in Ohio and neighboring states using monthly 1-hour sessions via Zoom. According to Dr. Kobau, “Of those 164 primary care providers, 97% reported higher interest in improving their care of patients with epilepsy, and at least 98% reported that they were more confident in treating their patients with epilepsy.” Since that time, over 900 providers have received the training, which now attracts participants from all over the country.
Although the current burden of managing epilepsy now seems to be falling heavily on primary care providers, Dr. Lado said he believes they can provide useful insight into their patients’ history and needs: “I think they are in a unique and impactful position, mostly to refer those patients who are still having seizures.”
Additional Resources for Patients and Providers
- American Academy of Pediatrics National Coordinating Center for Epilepsy
- American Epilepsy Society (CME courses designed to designed to increase knowledge about epilepsy diagnosis, treatment, and management; seizure first-aid; epilepsy stigma; and social determinants of health for people with epilepsy)
- Centers for Disease Control and Prevention .
Dr. Joshi, Dr. Kobau, and Dr. Lado report no relevant financial relationships.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.
A version of this article appeared on Medscape.com .
The Centers for Disease Control and Prevention (CDC) estimates that 1.1% of US adults have epilepsy. Although 89% report seeing a physician in the past year about their condition, only 62% of adults saw a neurologist or seizure specialist.
These findings prompted Rosemary Kobau, MPH, the acting team lead for the CDC’s epilepsy program, to take a closer look at referral patterns by primary care providers in the United States.
She also noticed what she calls a “big red flag”: “We found that 40% of primary care providers did not indicate that they would refer their patient with epilepsy to a neurologist when their patient fails to respond to treatment, or if they have a change in seizure activity,” Dr. Kobau told this news organization. Individuals with uncontrolled seizures are at risk for multiple adverse health outcomes, along with emotional problems, social stigma, and decreased life expectancy.
Factors that influenced primary care clinicians to refer to a neurologist included prompt availability of appointments, ability to talk to the neurologist, and whether a patient’s insurance covered specialty visits. Proximity of a specialist also was cited as a barrier, because neurologists can be hard to find outside of urban centers.
Wait lists for neurologist are not like to get shorter any time soon, according to a 2019 report from the American Academy of Neurology (AAN). A 2013 workforce report from the AAN found 35 US states, representing 62% of the US population, had fewer neurologists than needed to meet demand. By 2025, demand is projected to exceed supply in 41 states.
Much of the increasing demand for adult neurologists is driven by aging of the population, resulting in higher rates of stroke, Parkinson’s disease, and dementia. But pediatric neurologists are also overwhelmed: Pediatric neurology is one of the top three pediatric subspecialties with the longest wait times. The shortage is exacerbated by difficulties in transitioning adolescents with epilepsy — many diagnosed early in life with neurodevelopmental and epileptic encephalopathy and problem lists that include learning disorders, behavioral issues, and other chronic medical problems — to adult epilepsy specialists.
Although one of the solutions offered by the AAN is more training in epilepsy management for non-neurologists (such as CME programs developed by the American Epilepsy Society), many primary care providers are overwhelmed already. Still, primary care providers are well-positioned to help answer some of the most important questions about the management of patients with seizure disorders.
How to Help
“There’s a lot the pediatrician can do when a child presents with seizures,” said Sucheta Joshi, MD, who serves as the medical director of the Neurological Institute Comprehensive Epilepsy Center at Children’s Hospital Los Angeles.
Step one is helping to allay the fears of family members who witness a seizure. “They can talk about seizure safety, they can talk about first aid when a seizure happens, they can talk about what to do, what not to do,” she advised. Clinicians who see children can find resources for families on the American Academy of Pediatrics (AAP) National Coordinating Center for Epilepsy website, including a 24/7 helpline, information about local chapters of the Epilepsy Foundation, and first aid training for seizures.
Fred Lado, MD, PhD, a professor of neurology at the Zucker School of Medicine at Hofstra-Norwell in Hempstead, New York, said that primary care clinicians have several decision points when it comes to their patients with epilepsy.
The first is whether to initiate medication after the first episode of seizure. Studies show that the risk for a second seizure decreases in patients started on anticonvulsant therapy after a first event, but many clinicians don›t want to commit patients to long-term therapy without more evidence that the patient has epilepsy. Studies have shown that delaying therapy until a second seizure occurs doesn›t negatively affect quality of life and long-term prognosis.
The International League Against Epilepsy (ILAE) advised treatment for patients with two or more unprovoked seizures but revised its recommendation in 2014 to begin treatment after a first seizure for individuals at high risk for a second seizure. History of a brain insult related to a stroke, mass lesion in the brain, or trauma are risk factors for a second seizure, whereas seizures provoked by a concussion, alcohol withdrawal, or exposure to toxins carry low risk for additional episodes.
Dr. Lado also raised the importance of taking a good history from a patient presenting for medical care for a new-onset seizure to determine whether the recent episode is really the first such incident.
Up to half of patients presenting to emergency departments for convulsive seizures have a history of a preceding nonmotor seizure that the patient or their family members have failed to identify. As many as 60% of people with epilepsy have focal seizures, but the majority of these are nonmotor seizures. As a result, these patients often go without a diagnosis until they develop bilateral tonic-clonic seizures — by which time they may already been injured during a seizure or had an accident while driving.
In terms of imaging and other workup that should be performed prior to the first appointment with a pediatric neurologist or epilepsy specialist, Dr. Joshi generally recommends EEG. She also prefers MRI over CT, which is better for finding lesions that tend to cause seizures in kids such as developmental abnormalities like a cortical malformation or a perinatal process. Obtaining an MRI prior to seeing the neurologist is elective, depending on whether the history and clinical presentation suggest a focal lesion.
For adults, Dr. Lado also recommends an EEG and MRI to start but rarely advises other laboratory studies. When patients present to the emergency department with a new-onset seizure, the workup commonly includes a chemistry panel to rule out hypoglycemia or electrolyte abnormalities. But in the outpatient setting, where a patient describes symptoms of a seizure that occurred a week ago or longer, Dr. Lado said the yield of such assessments is low.
“I think the labs are often more useful as you’re thinking about an anticonvulsant,” Dr. Lado said. Particularly for a patient who is facing a long wait to see specialist, obtaining baseline liver enzymes and a complete blood cell count is worthwhile, because many antiseizure medications can cause anemia or liver damage.
Dr. Lado agreed that referral to a specialist is critical for patients with drug-resistant seizures, defined by the ILAE as seizures that persist despite the use of two or more anticonvulsants.
“One of the great problems in epilepsy care is a sort of sense of complacency,” he said. Some of his own patients have become comfortable with their epilepsy diagnosis and profess to be untroubled by having a few seizures per year. In 2018, Dr. Kobau was a co-author on a study reporting that less than half of US adults taking seizure medications were seizure-free in the past year.
This scenario is an opportunity for primary care providers to help determine whether their patients are taking their antiseizure medication correctly. A referral to a specialist might not be necessary if the seizures are occurring because the patient’s prescription ran out. Similarly, if a patient doesn’t take the medication because of unpleasant side effects, raising the dose won’t help.
Dr. Lado’s advice is to explore why the patient’s management plan is not working and make adjustments tailored to their needs. The solution might be as simple as changing the patient to an extended-release formulation to lower the number of daily doses needed, he said.
But for patients who do have recurrent seizures despite good adherence, Dr. Lado strongly urges a referral to an epilepsy specialist. He serves as president of the National Association of Epilepsy Centers (NAEC), a network of more than 260 epilepsy centers in the United States that offer the services of epileptologists, neurosurgeons, neuropsychologists, nurse specialists, EEG technologists, social workers, and others with training and experience in epilepsy care. In addition to adjusting and monitoring medications, patients seen at an NAEC can be evaluated for surgery, neurostimulators, and ketogenic diets.
Improving Self-Management
Another role that primary care can play is promoting self-efficacy among patients with epilepsy.
“Providers have historically tended to focus on medication adherence alone, ignoring other health enhancing behaviors, even just sleep hygiene,” Dr. Kobau said. But adequate sleep, regular exercise, a healthy diet, avoidance of tobacco and excessive alcohol, and stress management are all important for seizure management.
In 2007, CDC launched the Managing Epilepsy Well (MEW) Network, which has the mission of advancing self-management research in collaboration with patients with epilepsy as well as a broad range of healthcare providers. “It’s a patient-driven kind of approach consistent with community-based, participatory practice research,” said Dr. Kobau, who oversees the initiative.
The MEW network, which consists of six prevention research centers funded by CDC, has piloted and evaluated several evidence-based programs that can help patients better control their epilepsy.
One such intervention is Project Uplift, which delivers mindfulness-based cognitive-behavioral therapy in a virtual group setting. Behavioral therapy is important for people with seizure disorders, whose risk for depression is more than twice that of the general population. The initial trial found the intervention was effective in reducing depressive symptoms in participants, and research since has focused on adapting the program to provide culturally appropriate care to underserved populations. The eight sessions, held weekly, are available in both English and Spanish.
Another program, HOBSCOTCH, allows patients to meet one-on-one virtually with a trained coach to work on skills for improving attention and memory, common problems among people with epilepsy.
MINDSET involves a tablet-based clinical decision tool that patients can use to track their self-management behaviors, such as taking their medications, seizure triggers, symptoms of depression, and keeping their clinic appointments. It also helps them monitor whether they are getting adequate sleep, reducing their stress, and maintaining social networks. The tool generates a printable action plan for patients to prompt discussion and shared decision-making between patient and clinician to prioritize behavioral issues, set goals, and monitor changes over time.
Clinicians can refer patients to any of the MEW interventions, or patients can enroll themselves online.
Emerging Approaches
The AAN’s 2019 report promoted use of technological solutions to bridge the gap between primary care providers and scarce — as well as distant — neurologists. Many health systems support e-consults between clinicians, allowing simple discussions about medications and advice about testing recommended prior to a neurology visit. Initially developed for treatment for infection with hepatitis C virus, Project Extension for Community Healthcare Outcomes (ECHO) uses a central hub of specialists to support primary care providers via teleconference to conduct case reviews and didactic sessions.
Much of Dr. Joshi’s work has focused on ways to coordinate care to children who live far from a pediatric epilepsy center. In a previous position at the University of Michigan, her team was one of four sites funded by the AAP’s National Coordinating Center for Epilepsy to pilot an intervention using telehealth. Implemented in 2017-2019, the initiative used quality improvement methodology to explore a model where patients went to the office of their primary care provider so that both could participate in the call with a neurologist.
The strategy was successful, resulting in reduced out-of-pocket costs, missed school hours, and missed work hours. Patient satisfaction was high (97%), and more parents in the intervention group than the control group agreed that it was easier to obtain appointments with specialists (95% vs 65%, respectively).
And since the pandemic, in-home telehealth visits have become commonplace, adding to the potential convenience and cost savings of telemedicine.
CDC has invested in Project ECHO as a training program for nonspecialist providers to manage epilepsy. Based at the University of Cincinnati, the initial pilot from 2017 to 2019 trained primary care providers in Ohio and neighboring states using monthly 1-hour sessions via Zoom. According to Dr. Kobau, “Of those 164 primary care providers, 97% reported higher interest in improving their care of patients with epilepsy, and at least 98% reported that they were more confident in treating their patients with epilepsy.” Since that time, over 900 providers have received the training, which now attracts participants from all over the country.
Although the current burden of managing epilepsy now seems to be falling heavily on primary care providers, Dr. Lado said he believes they can provide useful insight into their patients’ history and needs: “I think they are in a unique and impactful position, mostly to refer those patients who are still having seizures.”
Additional Resources for Patients and Providers
- American Academy of Pediatrics National Coordinating Center for Epilepsy
- American Epilepsy Society (CME courses designed to designed to increase knowledge about epilepsy diagnosis, treatment, and management; seizure first-aid; epilepsy stigma; and social determinants of health for people with epilepsy)
- Centers for Disease Control and Prevention .
Dr. Joshi, Dr. Kobau, and Dr. Lado report no relevant financial relationships.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.
A version of this article appeared on Medscape.com .
The Centers for Disease Control and Prevention (CDC) estimates that 1.1% of US adults have epilepsy. Although 89% report seeing a physician in the past year about their condition, only 62% of adults saw a neurologist or seizure specialist.
These findings prompted Rosemary Kobau, MPH, the acting team lead for the CDC’s epilepsy program, to take a closer look at referral patterns by primary care providers in the United States.
She also noticed what she calls a “big red flag”: “We found that 40% of primary care providers did not indicate that they would refer their patient with epilepsy to a neurologist when their patient fails to respond to treatment, or if they have a change in seizure activity,” Dr. Kobau told this news organization. Individuals with uncontrolled seizures are at risk for multiple adverse health outcomes, along with emotional problems, social stigma, and decreased life expectancy.
Factors that influenced primary care clinicians to refer to a neurologist included prompt availability of appointments, ability to talk to the neurologist, and whether a patient’s insurance covered specialty visits. Proximity of a specialist also was cited as a barrier, because neurologists can be hard to find outside of urban centers.
Wait lists for neurologist are not like to get shorter any time soon, according to a 2019 report from the American Academy of Neurology (AAN). A 2013 workforce report from the AAN found 35 US states, representing 62% of the US population, had fewer neurologists than needed to meet demand. By 2025, demand is projected to exceed supply in 41 states.
Much of the increasing demand for adult neurologists is driven by aging of the population, resulting in higher rates of stroke, Parkinson’s disease, and dementia. But pediatric neurologists are also overwhelmed: Pediatric neurology is one of the top three pediatric subspecialties with the longest wait times. The shortage is exacerbated by difficulties in transitioning adolescents with epilepsy — many diagnosed early in life with neurodevelopmental and epileptic encephalopathy and problem lists that include learning disorders, behavioral issues, and other chronic medical problems — to adult epilepsy specialists.
Although one of the solutions offered by the AAN is more training in epilepsy management for non-neurologists (such as CME programs developed by the American Epilepsy Society), many primary care providers are overwhelmed already. Still, primary care providers are well-positioned to help answer some of the most important questions about the management of patients with seizure disorders.
How to Help
“There’s a lot the pediatrician can do when a child presents with seizures,” said Sucheta Joshi, MD, who serves as the medical director of the Neurological Institute Comprehensive Epilepsy Center at Children’s Hospital Los Angeles.
Step one is helping to allay the fears of family members who witness a seizure. “They can talk about seizure safety, they can talk about first aid when a seizure happens, they can talk about what to do, what not to do,” she advised. Clinicians who see children can find resources for families on the American Academy of Pediatrics (AAP) National Coordinating Center for Epilepsy website, including a 24/7 helpline, information about local chapters of the Epilepsy Foundation, and first aid training for seizures.
Fred Lado, MD, PhD, a professor of neurology at the Zucker School of Medicine at Hofstra-Norwell in Hempstead, New York, said that primary care clinicians have several decision points when it comes to their patients with epilepsy.
The first is whether to initiate medication after the first episode of seizure. Studies show that the risk for a second seizure decreases in patients started on anticonvulsant therapy after a first event, but many clinicians don›t want to commit patients to long-term therapy without more evidence that the patient has epilepsy. Studies have shown that delaying therapy until a second seizure occurs doesn›t negatively affect quality of life and long-term prognosis.
The International League Against Epilepsy (ILAE) advised treatment for patients with two or more unprovoked seizures but revised its recommendation in 2014 to begin treatment after a first seizure for individuals at high risk for a second seizure. History of a brain insult related to a stroke, mass lesion in the brain, or trauma are risk factors for a second seizure, whereas seizures provoked by a concussion, alcohol withdrawal, or exposure to toxins carry low risk for additional episodes.
Dr. Lado also raised the importance of taking a good history from a patient presenting for medical care for a new-onset seizure to determine whether the recent episode is really the first such incident.
Up to half of patients presenting to emergency departments for convulsive seizures have a history of a preceding nonmotor seizure that the patient or their family members have failed to identify. As many as 60% of people with epilepsy have focal seizures, but the majority of these are nonmotor seizures. As a result, these patients often go without a diagnosis until they develop bilateral tonic-clonic seizures — by which time they may already been injured during a seizure or had an accident while driving.
In terms of imaging and other workup that should be performed prior to the first appointment with a pediatric neurologist or epilepsy specialist, Dr. Joshi generally recommends EEG. She also prefers MRI over CT, which is better for finding lesions that tend to cause seizures in kids such as developmental abnormalities like a cortical malformation or a perinatal process. Obtaining an MRI prior to seeing the neurologist is elective, depending on whether the history and clinical presentation suggest a focal lesion.
For adults, Dr. Lado also recommends an EEG and MRI to start but rarely advises other laboratory studies. When patients present to the emergency department with a new-onset seizure, the workup commonly includes a chemistry panel to rule out hypoglycemia or electrolyte abnormalities. But in the outpatient setting, where a patient describes symptoms of a seizure that occurred a week ago or longer, Dr. Lado said the yield of such assessments is low.
“I think the labs are often more useful as you’re thinking about an anticonvulsant,” Dr. Lado said. Particularly for a patient who is facing a long wait to see specialist, obtaining baseline liver enzymes and a complete blood cell count is worthwhile, because many antiseizure medications can cause anemia or liver damage.
Dr. Lado agreed that referral to a specialist is critical for patients with drug-resistant seizures, defined by the ILAE as seizures that persist despite the use of two or more anticonvulsants.
“One of the great problems in epilepsy care is a sort of sense of complacency,” he said. Some of his own patients have become comfortable with their epilepsy diagnosis and profess to be untroubled by having a few seizures per year. In 2018, Dr. Kobau was a co-author on a study reporting that less than half of US adults taking seizure medications were seizure-free in the past year.
This scenario is an opportunity for primary care providers to help determine whether their patients are taking their antiseizure medication correctly. A referral to a specialist might not be necessary if the seizures are occurring because the patient’s prescription ran out. Similarly, if a patient doesn’t take the medication because of unpleasant side effects, raising the dose won’t help.
Dr. Lado’s advice is to explore why the patient’s management plan is not working and make adjustments tailored to their needs. The solution might be as simple as changing the patient to an extended-release formulation to lower the number of daily doses needed, he said.
But for patients who do have recurrent seizures despite good adherence, Dr. Lado strongly urges a referral to an epilepsy specialist. He serves as president of the National Association of Epilepsy Centers (NAEC), a network of more than 260 epilepsy centers in the United States that offer the services of epileptologists, neurosurgeons, neuropsychologists, nurse specialists, EEG technologists, social workers, and others with training and experience in epilepsy care. In addition to adjusting and monitoring medications, patients seen at an NAEC can be evaluated for surgery, neurostimulators, and ketogenic diets.
Improving Self-Management
Another role that primary care can play is promoting self-efficacy among patients with epilepsy.
“Providers have historically tended to focus on medication adherence alone, ignoring other health enhancing behaviors, even just sleep hygiene,” Dr. Kobau said. But adequate sleep, regular exercise, a healthy diet, avoidance of tobacco and excessive alcohol, and stress management are all important for seizure management.
In 2007, CDC launched the Managing Epilepsy Well (MEW) Network, which has the mission of advancing self-management research in collaboration with patients with epilepsy as well as a broad range of healthcare providers. “It’s a patient-driven kind of approach consistent with community-based, participatory practice research,” said Dr. Kobau, who oversees the initiative.
The MEW network, which consists of six prevention research centers funded by CDC, has piloted and evaluated several evidence-based programs that can help patients better control their epilepsy.
One such intervention is Project Uplift, which delivers mindfulness-based cognitive-behavioral therapy in a virtual group setting. Behavioral therapy is important for people with seizure disorders, whose risk for depression is more than twice that of the general population. The initial trial found the intervention was effective in reducing depressive symptoms in participants, and research since has focused on adapting the program to provide culturally appropriate care to underserved populations. The eight sessions, held weekly, are available in both English and Spanish.
Another program, HOBSCOTCH, allows patients to meet one-on-one virtually with a trained coach to work on skills for improving attention and memory, common problems among people with epilepsy.
MINDSET involves a tablet-based clinical decision tool that patients can use to track their self-management behaviors, such as taking their medications, seizure triggers, symptoms of depression, and keeping their clinic appointments. It also helps them monitor whether they are getting adequate sleep, reducing their stress, and maintaining social networks. The tool generates a printable action plan for patients to prompt discussion and shared decision-making between patient and clinician to prioritize behavioral issues, set goals, and monitor changes over time.
Clinicians can refer patients to any of the MEW interventions, or patients can enroll themselves online.
Emerging Approaches
The AAN’s 2019 report promoted use of technological solutions to bridge the gap between primary care providers and scarce — as well as distant — neurologists. Many health systems support e-consults between clinicians, allowing simple discussions about medications and advice about testing recommended prior to a neurology visit. Initially developed for treatment for infection with hepatitis C virus, Project Extension for Community Healthcare Outcomes (ECHO) uses a central hub of specialists to support primary care providers via teleconference to conduct case reviews and didactic sessions.
Much of Dr. Joshi’s work has focused on ways to coordinate care to children who live far from a pediatric epilepsy center. In a previous position at the University of Michigan, her team was one of four sites funded by the AAP’s National Coordinating Center for Epilepsy to pilot an intervention using telehealth. Implemented in 2017-2019, the initiative used quality improvement methodology to explore a model where patients went to the office of their primary care provider so that both could participate in the call with a neurologist.
The strategy was successful, resulting in reduced out-of-pocket costs, missed school hours, and missed work hours. Patient satisfaction was high (97%), and more parents in the intervention group than the control group agreed that it was easier to obtain appointments with specialists (95% vs 65%, respectively).
And since the pandemic, in-home telehealth visits have become commonplace, adding to the potential convenience and cost savings of telemedicine.
CDC has invested in Project ECHO as a training program for nonspecialist providers to manage epilepsy. Based at the University of Cincinnati, the initial pilot from 2017 to 2019 trained primary care providers in Ohio and neighboring states using monthly 1-hour sessions via Zoom. According to Dr. Kobau, “Of those 164 primary care providers, 97% reported higher interest in improving their care of patients with epilepsy, and at least 98% reported that they were more confident in treating their patients with epilepsy.” Since that time, over 900 providers have received the training, which now attracts participants from all over the country.
Although the current burden of managing epilepsy now seems to be falling heavily on primary care providers, Dr. Lado said he believes they can provide useful insight into their patients’ history and needs: “I think they are in a unique and impactful position, mostly to refer those patients who are still having seizures.”
Additional Resources for Patients and Providers
- American Academy of Pediatrics National Coordinating Center for Epilepsy
- American Epilepsy Society (CME courses designed to designed to increase knowledge about epilepsy diagnosis, treatment, and management; seizure first-aid; epilepsy stigma; and social determinants of health for people with epilepsy)
- Centers for Disease Control and Prevention .
Dr. Joshi, Dr. Kobau, and Dr. Lado report no relevant financial relationships.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.
A version of this article appeared on Medscape.com .
Eosinophilic Esophagitis: 5 Things to Know
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that affects both children and adults. EoE is defined by symptoms of esophageal dysfunction (eg, dysphagia, vomiting, difficulty in feeding), with presentation varying depending on patient age.
The global incidence of EoE has increased in recent decades. In the United States alone, EoE is estimated to affect approximately 150,000 people and result in as much as $1.4 billion in annual healthcare costs.
There currently is no clear treatment hierarchy for EoE, and long delays between symptom onset and diagnoses are common.
Still, the knowledge base surrounding the disease is growing, and existing interventions have shown tremendous success at curbing symptoms and disease progression.
To help clinicians stay up to date on the latest information on this debilitating disease, here are five things to know about EoE.
1. EoE prevalence is increasing although not consistently around the globe.
EoE was first recognized as a distinct clinical entity in the early 1990s, when it was considered a relatively rare disease. Now, the incidence and prevalence rates of EoE are escalating at rates that cannot be explained by increased disease awareness and detection.
Although EoE has been diagnosed in Latin America, the Middle East, and Asia, such instances are relatively uncommon in comparison with the spiking rates noted in the United States; in Western Europe, including Denmark, the Netherlands, and Switzerland; and in Australia.
Emerging data suggest that climate and location may be a factor in the varying incidence rates of EoE. An analysis of 233,649 patients in a US pathology database reported that EoE was more common in cold and arid climate zones than in tropical zones. Another study suggests that EoE is more common in low-density, rural environments compared with urban settings.
2. Environmental and food exposures may trigger EoE, and genetics probably play a role.
The unequal geographic distribution of EoE lends credence to the theory that external triggers, which naturally differ in various locales, play an outsized role in its development.
Mice studies have indicated that the inhalation of allergens induces notable eosinophil infiltration and degranulation, and a pilot study conducted in New York City found that EoE symptoms peaked during the July-to-September period when grass pollen counts were at their highest.
Early-life factors that can result in alteration to the microbiome have also been identified as possibly influencing EoE development. They include cesarean delivery, preterm delivery, admission to a neonatal intensive care unit, infant formula use, and maternal or infant use of antibiotics. Conversely, evidence suggests that Helicobacter pylori infection may be protective against EoE due to immunomodulating effects that have not yet been sufficiently identified in the literature.
Yet, the clearest association between EoE and outside triggers is found with food exposures. In one analysis of pediatric patients, the items that were most commonly associated with elevated food-specific serum immunoglobulin E antibodies in patients with EoE were milk (78%), wheat (69%), eggs (64%), peanuts (54%), and soy (51%). Food allergies are also on the uptick in countries with rising EoE rates, suggesting that the two trends may be interrelated.
From a genetic standpoint, EoE is more likely to develop in those with first-degree relatives with the disease than in the general population. Thirty independent genes thought to be associated with EoE have been identified. EoE is also significantly more common in men than in women.
3. Diagnosis requires knowing the symptoms, excluding other disorders, and performing biopsy.
EoE can occur early in life, with approximately one third of children with the disease presenting under age 5 years. The prevalence rises with age, eventually peaking in those aged 35-45 years.
The presentation of EoE can be quite variable depending on patient age. Pediatric patients are significantly more likely to experience failure to thrive, vomiting, and heartburn, whereas their adult counterparts more often present with food impaction and dysphagia.
At the 2018 AGREE international consensus conference, researchers defined diagnostic criteria as presence of esophageal dysfunction symptoms; exclusion of non-EoE disorders, such as gastroesophageal reflux disease and achalasia; and esophageal biopsy findings of at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2).
Endoscopic findings can also be crucial in diagnosing EoE because patients with this disease often present with inflammatory patterns recognizable in the form of exudates, furrows, and edema and/or fibrotic phenotypes such as the presence of rings and stenosis. Clinicians are advised to refer to the Endoscopic Reference Score proposed by Hirano and colleagues.
4. Treatment approaches rely on the ‘3 Ds.’
Although there is currently no leading strategy for the primary treatment of EoE, clinicians can avail themselves of suggested pathways.
The lack of a treatment hierarchy means that patients typically are very involved in selecting the therapy that works best for them. Physicians should be aware that patients researching EoE on their own might not find the information they need. A recent study found that the artificial intelligence tool ChatGPT was highly inaccurate when it came to providing answers about EoE.
The treatment strategies that clinicians and their patients can choose from revolve around the “3 Ds”: diet, drugs, and dilation.
Diet:
Three dietary interventions are available for EoE treatment:
- Elemental diet, in which patients consume only an amino-acid based formula that does not include any intact proteins
- Empiric elimination diet, which removes foods more commonly associated with food allergy regardless of whether there has been a positive allergy testing result
- Allergy testing-directed food elimination, which involves avoidance of all foods for which specific antibodies were detected or that tested positive on skin-prick tests
Each of these dietary interventions has clear advantages and drawbacks that should be discussed with patients. Elemental diets achieve robust histologic responses, yet their highly restrictive nature makes compliance difficult and can greatly impair patients’ quality of life.
Empiric elimination diets are the most popular choice and have shown high response rates. A common approach is to begin by removing six common foods (milk, wheat, egg, soy, nuts, and fish/seafood), which are then gradually reintroduced to identify the culprits. However, patients must be motivated to follow this process, and the likelihood it will be successful is greatly enhanced with assistance from a dietitian, which may not always be possible.
Last, allergy testing-guided food elimination diets have been reported to produce remissions rates of just under 50%, and the skin allergy tests they primarily rely on have been criticized for being unreliable.
Drugs:
The treatment of EoE experienced a significant advance in 2022 when dupilumab, a monoclonal antibody that binds to the interleukin (IL)–4 receptor alpha, became the first drug approved by the US Food and Drug Administration (FDA) for treating EoE in adults and pediatric patients aged 12 years or older. The drug was approved by the European Commission in 2023. In late January 2024, the FDA expanded dupilumab’s approval to children aged 1-11 years and weighing ≥ 15 kg after positive histologic remission and safety results were reported in the two-part phase 3 EoE KIDS trial.
In addition, the FDA approved budesonide, the first oral treatment for EoE, in February 2024.
These approvals have expanded treatment options beyond proton pump inhibitors (PPIs) and topical glucocorticosteroids, both of which received only nuanced recommendations for use under US and UK clinical guidelines.
A recent meta-analysis found that PPIs, off-label and EoE-specific topical steroids, and biologics had greater efficacy than did placebo in achieving histological remission. However, significant heterogeneity in the included studies’ eligibility criteria and outcome measures prevented development of a “solid therapeutic hierarchy,” the authors noted.
In addition, researchers are investigating therapies targeting IL-5 (eg, mepolizumab, reslizumab, and benralizumab) and other key inflammatory mediators in EoE, such as Siglec-8 (lirentelimab), IL-13 (cendakimab), and the sphingosine 1–phosphate receptor (etrasimod).
Dilation:
Finally, patients with significant strictures can benefit from dilation performed via through-the-scope balloons or Savary-Gilliard bougies, which can significantly and immediately improve symptoms even if they cannot address the underlying inflammation. Concerns that dilation would lead to increased complications, such as perforation and mucosal tears, do not appear to be borne out by recent data.
5. Reducing diagnosis delays is crucial for limiting EoE-associated morbidity.
Despite efforts to bring attention to EoE, evidence suggests that delays between symptom onset and diagnosis are common, and result in treatment delays. One study found a median lag time of 6 years.
The longer the delay in treatment, the more likely patients are to develop esophageal rings, a long narrowing in the esophageal caliber, or focal strictures. For example, diagnostic delays of more than 20 years result in prevalence rates of 70.8% for esophageal strictures, compared with 17.2% with delays of 0-2 years.
Simply put, the sooner one can identify EoE and begin treatment, the more likely patients are to be spared its worst effects.
A version of this article appeared on Medscape.com.
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that affects both children and adults. EoE is defined by symptoms of esophageal dysfunction (eg, dysphagia, vomiting, difficulty in feeding), with presentation varying depending on patient age.
The global incidence of EoE has increased in recent decades. In the United States alone, EoE is estimated to affect approximately 150,000 people and result in as much as $1.4 billion in annual healthcare costs.
There currently is no clear treatment hierarchy for EoE, and long delays between symptom onset and diagnoses are common.
Still, the knowledge base surrounding the disease is growing, and existing interventions have shown tremendous success at curbing symptoms and disease progression.
To help clinicians stay up to date on the latest information on this debilitating disease, here are five things to know about EoE.
1. EoE prevalence is increasing although not consistently around the globe.
EoE was first recognized as a distinct clinical entity in the early 1990s, when it was considered a relatively rare disease. Now, the incidence and prevalence rates of EoE are escalating at rates that cannot be explained by increased disease awareness and detection.
Although EoE has been diagnosed in Latin America, the Middle East, and Asia, such instances are relatively uncommon in comparison with the spiking rates noted in the United States; in Western Europe, including Denmark, the Netherlands, and Switzerland; and in Australia.
Emerging data suggest that climate and location may be a factor in the varying incidence rates of EoE. An analysis of 233,649 patients in a US pathology database reported that EoE was more common in cold and arid climate zones than in tropical zones. Another study suggests that EoE is more common in low-density, rural environments compared with urban settings.
2. Environmental and food exposures may trigger EoE, and genetics probably play a role.
The unequal geographic distribution of EoE lends credence to the theory that external triggers, which naturally differ in various locales, play an outsized role in its development.
Mice studies have indicated that the inhalation of allergens induces notable eosinophil infiltration and degranulation, and a pilot study conducted in New York City found that EoE symptoms peaked during the July-to-September period when grass pollen counts were at their highest.
Early-life factors that can result in alteration to the microbiome have also been identified as possibly influencing EoE development. They include cesarean delivery, preterm delivery, admission to a neonatal intensive care unit, infant formula use, and maternal or infant use of antibiotics. Conversely, evidence suggests that Helicobacter pylori infection may be protective against EoE due to immunomodulating effects that have not yet been sufficiently identified in the literature.
Yet, the clearest association between EoE and outside triggers is found with food exposures. In one analysis of pediatric patients, the items that were most commonly associated with elevated food-specific serum immunoglobulin E antibodies in patients with EoE were milk (78%), wheat (69%), eggs (64%), peanuts (54%), and soy (51%). Food allergies are also on the uptick in countries with rising EoE rates, suggesting that the two trends may be interrelated.
From a genetic standpoint, EoE is more likely to develop in those with first-degree relatives with the disease than in the general population. Thirty independent genes thought to be associated with EoE have been identified. EoE is also significantly more common in men than in women.
3. Diagnosis requires knowing the symptoms, excluding other disorders, and performing biopsy.
EoE can occur early in life, with approximately one third of children with the disease presenting under age 5 years. The prevalence rises with age, eventually peaking in those aged 35-45 years.
The presentation of EoE can be quite variable depending on patient age. Pediatric patients are significantly more likely to experience failure to thrive, vomiting, and heartburn, whereas their adult counterparts more often present with food impaction and dysphagia.
At the 2018 AGREE international consensus conference, researchers defined diagnostic criteria as presence of esophageal dysfunction symptoms; exclusion of non-EoE disorders, such as gastroesophageal reflux disease and achalasia; and esophageal biopsy findings of at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2).
Endoscopic findings can also be crucial in diagnosing EoE because patients with this disease often present with inflammatory patterns recognizable in the form of exudates, furrows, and edema and/or fibrotic phenotypes such as the presence of rings and stenosis. Clinicians are advised to refer to the Endoscopic Reference Score proposed by Hirano and colleagues.
4. Treatment approaches rely on the ‘3 Ds.’
Although there is currently no leading strategy for the primary treatment of EoE, clinicians can avail themselves of suggested pathways.
The lack of a treatment hierarchy means that patients typically are very involved in selecting the therapy that works best for them. Physicians should be aware that patients researching EoE on their own might not find the information they need. A recent study found that the artificial intelligence tool ChatGPT was highly inaccurate when it came to providing answers about EoE.
The treatment strategies that clinicians and their patients can choose from revolve around the “3 Ds”: diet, drugs, and dilation.
Diet:
Three dietary interventions are available for EoE treatment:
- Elemental diet, in which patients consume only an amino-acid based formula that does not include any intact proteins
- Empiric elimination diet, which removes foods more commonly associated with food allergy regardless of whether there has been a positive allergy testing result
- Allergy testing-directed food elimination, which involves avoidance of all foods for which specific antibodies were detected or that tested positive on skin-prick tests
Each of these dietary interventions has clear advantages and drawbacks that should be discussed with patients. Elemental diets achieve robust histologic responses, yet their highly restrictive nature makes compliance difficult and can greatly impair patients’ quality of life.
Empiric elimination diets are the most popular choice and have shown high response rates. A common approach is to begin by removing six common foods (milk, wheat, egg, soy, nuts, and fish/seafood), which are then gradually reintroduced to identify the culprits. However, patients must be motivated to follow this process, and the likelihood it will be successful is greatly enhanced with assistance from a dietitian, which may not always be possible.
Last, allergy testing-guided food elimination diets have been reported to produce remissions rates of just under 50%, and the skin allergy tests they primarily rely on have been criticized for being unreliable.
Drugs:
The treatment of EoE experienced a significant advance in 2022 when dupilumab, a monoclonal antibody that binds to the interleukin (IL)–4 receptor alpha, became the first drug approved by the US Food and Drug Administration (FDA) for treating EoE in adults and pediatric patients aged 12 years or older. The drug was approved by the European Commission in 2023. In late January 2024, the FDA expanded dupilumab’s approval to children aged 1-11 years and weighing ≥ 15 kg after positive histologic remission and safety results were reported in the two-part phase 3 EoE KIDS trial.
In addition, the FDA approved budesonide, the first oral treatment for EoE, in February 2024.
These approvals have expanded treatment options beyond proton pump inhibitors (PPIs) and topical glucocorticosteroids, both of which received only nuanced recommendations for use under US and UK clinical guidelines.
A recent meta-analysis found that PPIs, off-label and EoE-specific topical steroids, and biologics had greater efficacy than did placebo in achieving histological remission. However, significant heterogeneity in the included studies’ eligibility criteria and outcome measures prevented development of a “solid therapeutic hierarchy,” the authors noted.
In addition, researchers are investigating therapies targeting IL-5 (eg, mepolizumab, reslizumab, and benralizumab) and other key inflammatory mediators in EoE, such as Siglec-8 (lirentelimab), IL-13 (cendakimab), and the sphingosine 1–phosphate receptor (etrasimod).
Dilation:
Finally, patients with significant strictures can benefit from dilation performed via through-the-scope balloons or Savary-Gilliard bougies, which can significantly and immediately improve symptoms even if they cannot address the underlying inflammation. Concerns that dilation would lead to increased complications, such as perforation and mucosal tears, do not appear to be borne out by recent data.
5. Reducing diagnosis delays is crucial for limiting EoE-associated morbidity.
Despite efforts to bring attention to EoE, evidence suggests that delays between symptom onset and diagnosis are common, and result in treatment delays. One study found a median lag time of 6 years.
The longer the delay in treatment, the more likely patients are to develop esophageal rings, a long narrowing in the esophageal caliber, or focal strictures. For example, diagnostic delays of more than 20 years result in prevalence rates of 70.8% for esophageal strictures, compared with 17.2% with delays of 0-2 years.
Simply put, the sooner one can identify EoE and begin treatment, the more likely patients are to be spared its worst effects.
A version of this article appeared on Medscape.com.
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that affects both children and adults. EoE is defined by symptoms of esophageal dysfunction (eg, dysphagia, vomiting, difficulty in feeding), with presentation varying depending on patient age.
The global incidence of EoE has increased in recent decades. In the United States alone, EoE is estimated to affect approximately 150,000 people and result in as much as $1.4 billion in annual healthcare costs.
There currently is no clear treatment hierarchy for EoE, and long delays between symptom onset and diagnoses are common.
Still, the knowledge base surrounding the disease is growing, and existing interventions have shown tremendous success at curbing symptoms and disease progression.
To help clinicians stay up to date on the latest information on this debilitating disease, here are five things to know about EoE.
1. EoE prevalence is increasing although not consistently around the globe.
EoE was first recognized as a distinct clinical entity in the early 1990s, when it was considered a relatively rare disease. Now, the incidence and prevalence rates of EoE are escalating at rates that cannot be explained by increased disease awareness and detection.
Although EoE has been diagnosed in Latin America, the Middle East, and Asia, such instances are relatively uncommon in comparison with the spiking rates noted in the United States; in Western Europe, including Denmark, the Netherlands, and Switzerland; and in Australia.
Emerging data suggest that climate and location may be a factor in the varying incidence rates of EoE. An analysis of 233,649 patients in a US pathology database reported that EoE was more common in cold and arid climate zones than in tropical zones. Another study suggests that EoE is more common in low-density, rural environments compared with urban settings.
2. Environmental and food exposures may trigger EoE, and genetics probably play a role.
The unequal geographic distribution of EoE lends credence to the theory that external triggers, which naturally differ in various locales, play an outsized role in its development.
Mice studies have indicated that the inhalation of allergens induces notable eosinophil infiltration and degranulation, and a pilot study conducted in New York City found that EoE symptoms peaked during the July-to-September period when grass pollen counts were at their highest.
Early-life factors that can result in alteration to the microbiome have also been identified as possibly influencing EoE development. They include cesarean delivery, preterm delivery, admission to a neonatal intensive care unit, infant formula use, and maternal or infant use of antibiotics. Conversely, evidence suggests that Helicobacter pylori infection may be protective against EoE due to immunomodulating effects that have not yet been sufficiently identified in the literature.
Yet, the clearest association between EoE and outside triggers is found with food exposures. In one analysis of pediatric patients, the items that were most commonly associated with elevated food-specific serum immunoglobulin E antibodies in patients with EoE were milk (78%), wheat (69%), eggs (64%), peanuts (54%), and soy (51%). Food allergies are also on the uptick in countries with rising EoE rates, suggesting that the two trends may be interrelated.
From a genetic standpoint, EoE is more likely to develop in those with first-degree relatives with the disease than in the general population. Thirty independent genes thought to be associated with EoE have been identified. EoE is also significantly more common in men than in women.
3. Diagnosis requires knowing the symptoms, excluding other disorders, and performing biopsy.
EoE can occur early in life, with approximately one third of children with the disease presenting under age 5 years. The prevalence rises with age, eventually peaking in those aged 35-45 years.
The presentation of EoE can be quite variable depending on patient age. Pediatric patients are significantly more likely to experience failure to thrive, vomiting, and heartburn, whereas their adult counterparts more often present with food impaction and dysphagia.
At the 2018 AGREE international consensus conference, researchers defined diagnostic criteria as presence of esophageal dysfunction symptoms; exclusion of non-EoE disorders, such as gastroesophageal reflux disease and achalasia; and esophageal biopsy findings of at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2).
Endoscopic findings can also be crucial in diagnosing EoE because patients with this disease often present with inflammatory patterns recognizable in the form of exudates, furrows, and edema and/or fibrotic phenotypes such as the presence of rings and stenosis. Clinicians are advised to refer to the Endoscopic Reference Score proposed by Hirano and colleagues.
4. Treatment approaches rely on the ‘3 Ds.’
Although there is currently no leading strategy for the primary treatment of EoE, clinicians can avail themselves of suggested pathways.
The lack of a treatment hierarchy means that patients typically are very involved in selecting the therapy that works best for them. Physicians should be aware that patients researching EoE on their own might not find the information they need. A recent study found that the artificial intelligence tool ChatGPT was highly inaccurate when it came to providing answers about EoE.
The treatment strategies that clinicians and their patients can choose from revolve around the “3 Ds”: diet, drugs, and dilation.
Diet:
Three dietary interventions are available for EoE treatment:
- Elemental diet, in which patients consume only an amino-acid based formula that does not include any intact proteins
- Empiric elimination diet, which removes foods more commonly associated with food allergy regardless of whether there has been a positive allergy testing result
- Allergy testing-directed food elimination, which involves avoidance of all foods for which specific antibodies were detected or that tested positive on skin-prick tests
Each of these dietary interventions has clear advantages and drawbacks that should be discussed with patients. Elemental diets achieve robust histologic responses, yet their highly restrictive nature makes compliance difficult and can greatly impair patients’ quality of life.
Empiric elimination diets are the most popular choice and have shown high response rates. A common approach is to begin by removing six common foods (milk, wheat, egg, soy, nuts, and fish/seafood), which are then gradually reintroduced to identify the culprits. However, patients must be motivated to follow this process, and the likelihood it will be successful is greatly enhanced with assistance from a dietitian, which may not always be possible.
Last, allergy testing-guided food elimination diets have been reported to produce remissions rates of just under 50%, and the skin allergy tests they primarily rely on have been criticized for being unreliable.
Drugs:
The treatment of EoE experienced a significant advance in 2022 when dupilumab, a monoclonal antibody that binds to the interleukin (IL)–4 receptor alpha, became the first drug approved by the US Food and Drug Administration (FDA) for treating EoE in adults and pediatric patients aged 12 years or older. The drug was approved by the European Commission in 2023. In late January 2024, the FDA expanded dupilumab’s approval to children aged 1-11 years and weighing ≥ 15 kg after positive histologic remission and safety results were reported in the two-part phase 3 EoE KIDS trial.
In addition, the FDA approved budesonide, the first oral treatment for EoE, in February 2024.
These approvals have expanded treatment options beyond proton pump inhibitors (PPIs) and topical glucocorticosteroids, both of which received only nuanced recommendations for use under US and UK clinical guidelines.
A recent meta-analysis found that PPIs, off-label and EoE-specific topical steroids, and biologics had greater efficacy than did placebo in achieving histological remission. However, significant heterogeneity in the included studies’ eligibility criteria and outcome measures prevented development of a “solid therapeutic hierarchy,” the authors noted.
In addition, researchers are investigating therapies targeting IL-5 (eg, mepolizumab, reslizumab, and benralizumab) and other key inflammatory mediators in EoE, such as Siglec-8 (lirentelimab), IL-13 (cendakimab), and the sphingosine 1–phosphate receptor (etrasimod).
Dilation:
Finally, patients with significant strictures can benefit from dilation performed via through-the-scope balloons or Savary-Gilliard bougies, which can significantly and immediately improve symptoms even if they cannot address the underlying inflammation. Concerns that dilation would lead to increased complications, such as perforation and mucosal tears, do not appear to be borne out by recent data.
5. Reducing diagnosis delays is crucial for limiting EoE-associated morbidity.
Despite efforts to bring attention to EoE, evidence suggests that delays between symptom onset and diagnosis are common, and result in treatment delays. One study found a median lag time of 6 years.
The longer the delay in treatment, the more likely patients are to develop esophageal rings, a long narrowing in the esophageal caliber, or focal strictures. For example, diagnostic delays of more than 20 years result in prevalence rates of 70.8% for esophageal strictures, compared with 17.2% with delays of 0-2 years.
Simply put, the sooner one can identify EoE and begin treatment, the more likely patients are to be spared its worst effects.
A version of this article appeared on Medscape.com.
How Primary Care Can Better Treat Chronic Pain
Jill Schneiderhan, MD, remembers only receiving one or two lectures on basic pain physiology during medical school.
That time was not enough, Dr. Schneiderhan said, who is now a primary care physician and codirector of Integrative Family Medicine at Michigan Medicine in Ann Arbor, Michigan. Medical schools in the United States spend an average of 11 hours on pain management training.
Despite one in five Americans experiencing chronic pain, a gap exists in the pain management training of primary care providers (PCPs). Pain specialists are calling for the empowerment of their first-line-of-defense counterparts with the knowledge and tools necessary to navigate the intricate challenges posed by chronic pain.
Treatment beyond medication is the primary challenge — particularly with pressures and time constraints inherent in family medicine.
“It’s so difficult to teach a PCP how to treat pain because pain management is an entire fellowship,” said Shravani Durbhakula, MD, MPH, MBA, who is on the Board of Directors for the American Academy of Pain Medicine Foundation. But “we encourage a multidisciplinary approach: This includes physical therapy, medication, injections, and other methods. Those different elements coming together typically give some relief.”
Categories of Chronic Pain
Experts sort pain into three broad categories: Nociceptive (from tissue injury), neuropathic (from a nerve injury), and nociplastic (from a sensitized nervous system).
Tissue injury is the most common cause of pain and is characterized by aching and throbbing, while nerve injury causes more burning and shooting sensations.
Nociplastic pain, which arises from abnormal processing of pain signals without clear evidence of tissue damage, is often hardest to understand and trickier to treat. These types of conditions include fibromyalgia, irritable bowel syndrome, and nonspecific back pain, according to Dr. Durbhakula.
“One of the really big challenges is that it’s an invisible condition — you don’t have a cast on or crutches,” Dr. Durbhakula said. “We don’t have great objective measures for pain, and sometimes pain patients feel stigmatized and like their pain is dismissed.”
Primary care specialists should consider six steps to guide their pain assessments, including properly assessing the pain, identifying the pain generator, discussing sensible medications, considering appropriate procedures, recommending appropriate behavioral techniques, and focusing on multidisciplinary management, according to Dr. Durbhakula.
Persistent pain is often too complex to treat with singular methods. For instance, studies have shown pain can lead to structural changes in the brain, such as a decrease in gray matter and differences in neural areas that modulate pain. These neurologic changes illustrate the complicated nature of chronic pain and the need for a multipronged treatment plan.
Don’t Discount the ‘Fluffy Stuff’
One of the biggest challenges in managing chronic pain is the dearth of effective remedies, said Michael Kaplan, MD, a rheumatologist at Mount Sinai Health System in New York City.
While other debilitating conditions have seen breakthroughs — insulin for diabetes, penicillin for pneumonia — pain remains without a cure.
“In the world of centralized pains, we’re lagging behind,” Dr. Kaplan said. “Opioids didn’t work, and here we are in the aftermath of an opioid epidemic.”
Patients can make significant headway with nonpharmacologic management, or what some consider to be the “fluffy stuff,” including yoga, meditation, acupuncture, dry needling, massage therapy, and acupuncture, according to Dr. Kaplan.
But these approaches are often financially unfeasible for patients because insurance companies sporadically cover them. However, free apps can help patients practice things like better sleep and meditation.
“These things actually work, and there is very low risk in trying them,” Dr. Kaplan said. To be sure, medication has an important place in pain management. Neuropathic pain medications or nonsteroidal anti-inflammatory drugs can be effective options for some patients, said Christopher Gilligan, MD, Chief of the Division of Pain Medicine at Brigham and Women’s Hospital in Boston, Massachusetts.
Drugs that target nerve pain include gabapentin and pregabalin, certain antidepressants, and anticonvulsants, which can help dull pain signals in the nerves.
“When a patient has not responded to a first- or second-line medication in those categories, that can be a time when referral to a pain medicine physician can be helpful,” Dr. Gilligan said.
Procedural options that are less invasive than surgery may also be appropriate, Dr. Gilligan said. These include nerve ablation and restorative neurostimulators for people with lower back pain and ganglion stimulation for patients experiencing neuropathic pain.
“The efficacy of interventions for specific pain conditions has gotten better over the years,” he said.
Learn to Listen
The two most important activities to recommend when treating chronic pain patients also can be the most difficult: Sleeping and exercise. For people experiencing unrelenting discomfort, both can feel impossible, according to Dan Clauw, MD, professor of anesthesiology at the University of Michigan in Ann Arbor, Michigan.
“If you stop moving, your pain is going to get worse and worse and worse,” Dr. Clauw said. “But you have to be careful about how you talk about it. For example, don’t use the word ‘exercise’ when you’re talking to a chronic pain patient, use the word ‘activity.’ ”
As people become more active, they begin sleeping better, he said.
Most importantly, Dr. Clauw said, clinicians must demonstrate empathy and listening skills. Patients with chronic pain often are used to being dismissed and have become isolated in their personal lives.
“There is a lack of properly trained providers who can listen rather than do procedures,” Dr. Clauw said. “What happens is people just constrict their lives over the course of having pain, and they fall into this shell of themselves. They need their doctors to hear them.”
For primary care doctors seeking more information on pain management, online resources can be helpful, said Robert L. Rich Jr, MD, former chair of the American Academy of Family Physicians Commission on Health of the Public and Science.
“One suggestion I’d begin with is to look at pain guidelines, not just from the CDC and AAFP but also from local medical boards,” Dr. Rich said, adding that California and Washington State have done extensive work on chronic pain. “I am seeing more of a movement again toward teaching the management of chronic pain, but we still need more training.”
A version of this article appeared on Medscape.com.
Jill Schneiderhan, MD, remembers only receiving one or two lectures on basic pain physiology during medical school.
That time was not enough, Dr. Schneiderhan said, who is now a primary care physician and codirector of Integrative Family Medicine at Michigan Medicine in Ann Arbor, Michigan. Medical schools in the United States spend an average of 11 hours on pain management training.
Despite one in five Americans experiencing chronic pain, a gap exists in the pain management training of primary care providers (PCPs). Pain specialists are calling for the empowerment of their first-line-of-defense counterparts with the knowledge and tools necessary to navigate the intricate challenges posed by chronic pain.
Treatment beyond medication is the primary challenge — particularly with pressures and time constraints inherent in family medicine.
“It’s so difficult to teach a PCP how to treat pain because pain management is an entire fellowship,” said Shravani Durbhakula, MD, MPH, MBA, who is on the Board of Directors for the American Academy of Pain Medicine Foundation. But “we encourage a multidisciplinary approach: This includes physical therapy, medication, injections, and other methods. Those different elements coming together typically give some relief.”
Categories of Chronic Pain
Experts sort pain into three broad categories: Nociceptive (from tissue injury), neuropathic (from a nerve injury), and nociplastic (from a sensitized nervous system).
Tissue injury is the most common cause of pain and is characterized by aching and throbbing, while nerve injury causes more burning and shooting sensations.
Nociplastic pain, which arises from abnormal processing of pain signals without clear evidence of tissue damage, is often hardest to understand and trickier to treat. These types of conditions include fibromyalgia, irritable bowel syndrome, and nonspecific back pain, according to Dr. Durbhakula.
“One of the really big challenges is that it’s an invisible condition — you don’t have a cast on or crutches,” Dr. Durbhakula said. “We don’t have great objective measures for pain, and sometimes pain patients feel stigmatized and like their pain is dismissed.”
Primary care specialists should consider six steps to guide their pain assessments, including properly assessing the pain, identifying the pain generator, discussing sensible medications, considering appropriate procedures, recommending appropriate behavioral techniques, and focusing on multidisciplinary management, according to Dr. Durbhakula.
Persistent pain is often too complex to treat with singular methods. For instance, studies have shown pain can lead to structural changes in the brain, such as a decrease in gray matter and differences in neural areas that modulate pain. These neurologic changes illustrate the complicated nature of chronic pain and the need for a multipronged treatment plan.
Don’t Discount the ‘Fluffy Stuff’
One of the biggest challenges in managing chronic pain is the dearth of effective remedies, said Michael Kaplan, MD, a rheumatologist at Mount Sinai Health System in New York City.
While other debilitating conditions have seen breakthroughs — insulin for diabetes, penicillin for pneumonia — pain remains without a cure.
“In the world of centralized pains, we’re lagging behind,” Dr. Kaplan said. “Opioids didn’t work, and here we are in the aftermath of an opioid epidemic.”
Patients can make significant headway with nonpharmacologic management, or what some consider to be the “fluffy stuff,” including yoga, meditation, acupuncture, dry needling, massage therapy, and acupuncture, according to Dr. Kaplan.
But these approaches are often financially unfeasible for patients because insurance companies sporadically cover them. However, free apps can help patients practice things like better sleep and meditation.
“These things actually work, and there is very low risk in trying them,” Dr. Kaplan said. To be sure, medication has an important place in pain management. Neuropathic pain medications or nonsteroidal anti-inflammatory drugs can be effective options for some patients, said Christopher Gilligan, MD, Chief of the Division of Pain Medicine at Brigham and Women’s Hospital in Boston, Massachusetts.
Drugs that target nerve pain include gabapentin and pregabalin, certain antidepressants, and anticonvulsants, which can help dull pain signals in the nerves.
“When a patient has not responded to a first- or second-line medication in those categories, that can be a time when referral to a pain medicine physician can be helpful,” Dr. Gilligan said.
Procedural options that are less invasive than surgery may also be appropriate, Dr. Gilligan said. These include nerve ablation and restorative neurostimulators for people with lower back pain and ganglion stimulation for patients experiencing neuropathic pain.
“The efficacy of interventions for specific pain conditions has gotten better over the years,” he said.
Learn to Listen
The two most important activities to recommend when treating chronic pain patients also can be the most difficult: Sleeping and exercise. For people experiencing unrelenting discomfort, both can feel impossible, according to Dan Clauw, MD, professor of anesthesiology at the University of Michigan in Ann Arbor, Michigan.
“If you stop moving, your pain is going to get worse and worse and worse,” Dr. Clauw said. “But you have to be careful about how you talk about it. For example, don’t use the word ‘exercise’ when you’re talking to a chronic pain patient, use the word ‘activity.’ ”
As people become more active, they begin sleeping better, he said.
Most importantly, Dr. Clauw said, clinicians must demonstrate empathy and listening skills. Patients with chronic pain often are used to being dismissed and have become isolated in their personal lives.
“There is a lack of properly trained providers who can listen rather than do procedures,” Dr. Clauw said. “What happens is people just constrict their lives over the course of having pain, and they fall into this shell of themselves. They need their doctors to hear them.”
For primary care doctors seeking more information on pain management, online resources can be helpful, said Robert L. Rich Jr, MD, former chair of the American Academy of Family Physicians Commission on Health of the Public and Science.
“One suggestion I’d begin with is to look at pain guidelines, not just from the CDC and AAFP but also from local medical boards,” Dr. Rich said, adding that California and Washington State have done extensive work on chronic pain. “I am seeing more of a movement again toward teaching the management of chronic pain, but we still need more training.”
A version of this article appeared on Medscape.com.
Jill Schneiderhan, MD, remembers only receiving one or two lectures on basic pain physiology during medical school.
That time was not enough, Dr. Schneiderhan said, who is now a primary care physician and codirector of Integrative Family Medicine at Michigan Medicine in Ann Arbor, Michigan. Medical schools in the United States spend an average of 11 hours on pain management training.
Despite one in five Americans experiencing chronic pain, a gap exists in the pain management training of primary care providers (PCPs). Pain specialists are calling for the empowerment of their first-line-of-defense counterparts with the knowledge and tools necessary to navigate the intricate challenges posed by chronic pain.
Treatment beyond medication is the primary challenge — particularly with pressures and time constraints inherent in family medicine.
“It’s so difficult to teach a PCP how to treat pain because pain management is an entire fellowship,” said Shravani Durbhakula, MD, MPH, MBA, who is on the Board of Directors for the American Academy of Pain Medicine Foundation. But “we encourage a multidisciplinary approach: This includes physical therapy, medication, injections, and other methods. Those different elements coming together typically give some relief.”
Categories of Chronic Pain
Experts sort pain into three broad categories: Nociceptive (from tissue injury), neuropathic (from a nerve injury), and nociplastic (from a sensitized nervous system).
Tissue injury is the most common cause of pain and is characterized by aching and throbbing, while nerve injury causes more burning and shooting sensations.
Nociplastic pain, which arises from abnormal processing of pain signals without clear evidence of tissue damage, is often hardest to understand and trickier to treat. These types of conditions include fibromyalgia, irritable bowel syndrome, and nonspecific back pain, according to Dr. Durbhakula.
“One of the really big challenges is that it’s an invisible condition — you don’t have a cast on or crutches,” Dr. Durbhakula said. “We don’t have great objective measures for pain, and sometimes pain patients feel stigmatized and like their pain is dismissed.”
Primary care specialists should consider six steps to guide their pain assessments, including properly assessing the pain, identifying the pain generator, discussing sensible medications, considering appropriate procedures, recommending appropriate behavioral techniques, and focusing on multidisciplinary management, according to Dr. Durbhakula.
Persistent pain is often too complex to treat with singular methods. For instance, studies have shown pain can lead to structural changes in the brain, such as a decrease in gray matter and differences in neural areas that modulate pain. These neurologic changes illustrate the complicated nature of chronic pain and the need for a multipronged treatment plan.
Don’t Discount the ‘Fluffy Stuff’
One of the biggest challenges in managing chronic pain is the dearth of effective remedies, said Michael Kaplan, MD, a rheumatologist at Mount Sinai Health System in New York City.
While other debilitating conditions have seen breakthroughs — insulin for diabetes, penicillin for pneumonia — pain remains without a cure.
“In the world of centralized pains, we’re lagging behind,” Dr. Kaplan said. “Opioids didn’t work, and here we are in the aftermath of an opioid epidemic.”
Patients can make significant headway with nonpharmacologic management, or what some consider to be the “fluffy stuff,” including yoga, meditation, acupuncture, dry needling, massage therapy, and acupuncture, according to Dr. Kaplan.
But these approaches are often financially unfeasible for patients because insurance companies sporadically cover them. However, free apps can help patients practice things like better sleep and meditation.
“These things actually work, and there is very low risk in trying them,” Dr. Kaplan said. To be sure, medication has an important place in pain management. Neuropathic pain medications or nonsteroidal anti-inflammatory drugs can be effective options for some patients, said Christopher Gilligan, MD, Chief of the Division of Pain Medicine at Brigham and Women’s Hospital in Boston, Massachusetts.
Drugs that target nerve pain include gabapentin and pregabalin, certain antidepressants, and anticonvulsants, which can help dull pain signals in the nerves.
“When a patient has not responded to a first- or second-line medication in those categories, that can be a time when referral to a pain medicine physician can be helpful,” Dr. Gilligan said.
Procedural options that are less invasive than surgery may also be appropriate, Dr. Gilligan said. These include nerve ablation and restorative neurostimulators for people with lower back pain and ganglion stimulation for patients experiencing neuropathic pain.
“The efficacy of interventions for specific pain conditions has gotten better over the years,” he said.
Learn to Listen
The two most important activities to recommend when treating chronic pain patients also can be the most difficult: Sleeping and exercise. For people experiencing unrelenting discomfort, both can feel impossible, according to Dan Clauw, MD, professor of anesthesiology at the University of Michigan in Ann Arbor, Michigan.
“If you stop moving, your pain is going to get worse and worse and worse,” Dr. Clauw said. “But you have to be careful about how you talk about it. For example, don’t use the word ‘exercise’ when you’re talking to a chronic pain patient, use the word ‘activity.’ ”
As people become more active, they begin sleeping better, he said.
Most importantly, Dr. Clauw said, clinicians must demonstrate empathy and listening skills. Patients with chronic pain often are used to being dismissed and have become isolated in their personal lives.
“There is a lack of properly trained providers who can listen rather than do procedures,” Dr. Clauw said. “What happens is people just constrict their lives over the course of having pain, and they fall into this shell of themselves. They need their doctors to hear them.”
For primary care doctors seeking more information on pain management, online resources can be helpful, said Robert L. Rich Jr, MD, former chair of the American Academy of Family Physicians Commission on Health of the Public and Science.
“One suggestion I’d begin with is to look at pain guidelines, not just from the CDC and AAFP but also from local medical boards,” Dr. Rich said, adding that California and Washington State have done extensive work on chronic pain. “I am seeing more of a movement again toward teaching the management of chronic pain, but we still need more training.”
A version of this article appeared on Medscape.com.
Postinfectious Cough: Are Treatments Ever Warranted?
Lingering postinfectious cough has been a concern across Canada this winter. , according to an overview published on February 12 in the Canadian Medical Association Journal
“It’s something a lot of patients are worried about: That lingering cough after a common cold or flu,” lead author Kevin Liang, MD, of the Department of Family Medicine at The University of British Columbia in Vancouver, British Columbia, Canada, told this news organization. He added that some studies show that as much as a quarter of adult patients have this complaint.
Dr. Liang and his colleagues emphasized that the diagnosis of postinfectious cough is one of exclusion. It relies on the absence of concerning physical examination findings and other “subacute cough mimics” such as asthma, chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease, or use of angiotensin-converting enzyme inhibitors.
“Pertussis should be considered in patients with a paroxysmal cough, post-tussive vomiting, and inspiratory whoop,” they added. Coughs that persist beyond 8 weeks warrant further workup such as a pulmonary function test to rule out asthma or COPD. Coughs accompanied by hemoptysis, systemic symptoms, dysphagia, excessive dyspnea, or hoarseness also warrant further workup, they added. And patients with a history of smoking or recurrent pneumonia should be followed more closely.
In the absence of red flags, Dr. Liang and coauthors advised that there is no evidence supporting pharmacologic treatment, “which is associated with harms,” such as medication adverse effects, cost, strain on the medical supply chain, and the fact that pressurized metered-dose inhalers emit powerful greenhouse gases. “A lot of patients come in looking for solutions, but really, all the evidence says the over-the-counter cough syrup just doesn’t work. Or I see clinicians prescribing inhalers or different medication that can cost hundreds of dollars, and their efficacy, at least from the literature, shows that there’s really no improvement. Time and patience are the two keys to solving this,” Dr. Liang told this news organization.
Moreover, there is a distinct absence of guidelines on this topic. The College of Family Physicians of Canada’s recent literature review cited limited data supporting a trial of inhaled corticosteroids, a bronchodilator such as ipratropium-salbutamol, or an intranasal steroid if postnasal drip is suspected. However, “there’s a high risk of bias in the study they cite from using the short-acting bronchodilators, and what it ultimately says is that in most cases, this is self-resolving by around the 20-day mark,” said Dr. Liang. “Our advice is just to err on the side of caution and just provide that information piece to the patient.”
‘Significant Nuance’
Imran Satia, MD, assistant professor of respirology at McMaster University in Hamilton, Ontario, Canada, agreed that “most people who get a viral or bacterial upper or lower respiratory tract infection will get better with time, and there is very little evidence that giving steroids, antibiotics, or cough suppressants is better than waiting it out.” There is “significant nuance” in how to manage this situation, however.
“In some patients with underlying lung disease like asthma or COPD, increasing the frequency of regular inhaled steroids, bronchodilators, oral steroids, antibiotics, and chest imaging with breathing tests may be clinically warranted, and many physicians will do this,” he told this news organization. “In some patients with refractory chronic cough, there is no underlying identifiable disease, despite completing the necessary investigations. Or coughing persists despite trials of treatment for lung diseases, nasal diseases, and stomach reflux disease. This is commonly described as cough hypersensitivity syndrome, for which therapies targeting the neuronal pathways that control coughing are needed.”
Physicians should occasionally consider trying a temporary course of a short-acting bronchodilator inhaler, said Nicholas Vozoris, MD, assistant professor and clinician investigator in respirology at the University of Toronto, Toronto, Ontario, Canada. “I think that would be a reasonable first step in a case of really bad postinfectious cough,” he told this news organization. “But in general, drug treatments are not indicated.”
Environmental Concerns
Yet some things should raise clinicians’ suspicion of more complex issues.
“A pattern of recurrent colds or bronchitis with protracted coughing afterward raises strong suspicion for asthma, which can present as repeated, prolonged respiratory exacerbations,” he said. “Unless asthma is treated with appropriate inhaler therapy on a regular basis, it will unlikely come under control.”
Dr. Vozoris added that the environmental concerns over the use of metered dose inhalers (MDIs) are minimal compared with the other sources of pollution and the risks for undertreatment. “The authors are overplaying the environmental impact of MDI, in my opinion,” he said. “Physicians already have to deal with the challenging issue of suboptimal patient adherence to inhalers, and I fear that such comments may further drive that up. Furthermore, there is also an environmental footprint with not using inhalers, as patients can then experience suboptimally controlled lung disease as a result — and then present to the ER and get admitted to hospital for exacerbations of disease, where more resources and medications are used up.”
“In addition, in patients who are immunocompromised, protracted coughing after what was thought to be a cold may be associated with an “atypical” respiratory infection, such as tuberculosis, that will require special medical treatment,” Dr. Vozoris concluded.
No funding for the review of postinfectious cough was reported. Dr. Liang and Dr. Vozoris disclosed no competing interests. Dr. Satia reported receiving funding from the ERS Respire 3 Fellowship Award, BMA James Trust Award, North-West Lung Centre Charity (Manchester), NIHR CRF Manchester, Merck MSD, AstraZeneca, and GSK. Dr. Satia also has received consulting fees from Merck MSD, Genentech, and Respiplus; as well as speaker fees from AstraZeneca, GSK, Merck MSD, Sanofi-Regeneron. Satia has served on the following task force committees: Chronic Cough (ERS), Asthma Diagnosis and Management (ERS), NEUROCOUGH (ERS CRC), and the CTS Chronic Cough working group.
A version of this article appeared on Medscape.com.
Lingering postinfectious cough has been a concern across Canada this winter. , according to an overview published on February 12 in the Canadian Medical Association Journal
“It’s something a lot of patients are worried about: That lingering cough after a common cold or flu,” lead author Kevin Liang, MD, of the Department of Family Medicine at The University of British Columbia in Vancouver, British Columbia, Canada, told this news organization. He added that some studies show that as much as a quarter of adult patients have this complaint.
Dr. Liang and his colleagues emphasized that the diagnosis of postinfectious cough is one of exclusion. It relies on the absence of concerning physical examination findings and other “subacute cough mimics” such as asthma, chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease, or use of angiotensin-converting enzyme inhibitors.
“Pertussis should be considered in patients with a paroxysmal cough, post-tussive vomiting, and inspiratory whoop,” they added. Coughs that persist beyond 8 weeks warrant further workup such as a pulmonary function test to rule out asthma or COPD. Coughs accompanied by hemoptysis, systemic symptoms, dysphagia, excessive dyspnea, or hoarseness also warrant further workup, they added. And patients with a history of smoking or recurrent pneumonia should be followed more closely.
In the absence of red flags, Dr. Liang and coauthors advised that there is no evidence supporting pharmacologic treatment, “which is associated with harms,” such as medication adverse effects, cost, strain on the medical supply chain, and the fact that pressurized metered-dose inhalers emit powerful greenhouse gases. “A lot of patients come in looking for solutions, but really, all the evidence says the over-the-counter cough syrup just doesn’t work. Or I see clinicians prescribing inhalers or different medication that can cost hundreds of dollars, and their efficacy, at least from the literature, shows that there’s really no improvement. Time and patience are the two keys to solving this,” Dr. Liang told this news organization.
Moreover, there is a distinct absence of guidelines on this topic. The College of Family Physicians of Canada’s recent literature review cited limited data supporting a trial of inhaled corticosteroids, a bronchodilator such as ipratropium-salbutamol, or an intranasal steroid if postnasal drip is suspected. However, “there’s a high risk of bias in the study they cite from using the short-acting bronchodilators, and what it ultimately says is that in most cases, this is self-resolving by around the 20-day mark,” said Dr. Liang. “Our advice is just to err on the side of caution and just provide that information piece to the patient.”
‘Significant Nuance’
Imran Satia, MD, assistant professor of respirology at McMaster University in Hamilton, Ontario, Canada, agreed that “most people who get a viral or bacterial upper or lower respiratory tract infection will get better with time, and there is very little evidence that giving steroids, antibiotics, or cough suppressants is better than waiting it out.” There is “significant nuance” in how to manage this situation, however.
“In some patients with underlying lung disease like asthma or COPD, increasing the frequency of regular inhaled steroids, bronchodilators, oral steroids, antibiotics, and chest imaging with breathing tests may be clinically warranted, and many physicians will do this,” he told this news organization. “In some patients with refractory chronic cough, there is no underlying identifiable disease, despite completing the necessary investigations. Or coughing persists despite trials of treatment for lung diseases, nasal diseases, and stomach reflux disease. This is commonly described as cough hypersensitivity syndrome, for which therapies targeting the neuronal pathways that control coughing are needed.”
Physicians should occasionally consider trying a temporary course of a short-acting bronchodilator inhaler, said Nicholas Vozoris, MD, assistant professor and clinician investigator in respirology at the University of Toronto, Toronto, Ontario, Canada. “I think that would be a reasonable first step in a case of really bad postinfectious cough,” he told this news organization. “But in general, drug treatments are not indicated.”
Environmental Concerns
Yet some things should raise clinicians’ suspicion of more complex issues.
“A pattern of recurrent colds or bronchitis with protracted coughing afterward raises strong suspicion for asthma, which can present as repeated, prolonged respiratory exacerbations,” he said. “Unless asthma is treated with appropriate inhaler therapy on a regular basis, it will unlikely come under control.”
Dr. Vozoris added that the environmental concerns over the use of metered dose inhalers (MDIs) are minimal compared with the other sources of pollution and the risks for undertreatment. “The authors are overplaying the environmental impact of MDI, in my opinion,” he said. “Physicians already have to deal with the challenging issue of suboptimal patient adherence to inhalers, and I fear that such comments may further drive that up. Furthermore, there is also an environmental footprint with not using inhalers, as patients can then experience suboptimally controlled lung disease as a result — and then present to the ER and get admitted to hospital for exacerbations of disease, where more resources and medications are used up.”
“In addition, in patients who are immunocompromised, protracted coughing after what was thought to be a cold may be associated with an “atypical” respiratory infection, such as tuberculosis, that will require special medical treatment,” Dr. Vozoris concluded.
No funding for the review of postinfectious cough was reported. Dr. Liang and Dr. Vozoris disclosed no competing interests. Dr. Satia reported receiving funding from the ERS Respire 3 Fellowship Award, BMA James Trust Award, North-West Lung Centre Charity (Manchester), NIHR CRF Manchester, Merck MSD, AstraZeneca, and GSK. Dr. Satia also has received consulting fees from Merck MSD, Genentech, and Respiplus; as well as speaker fees from AstraZeneca, GSK, Merck MSD, Sanofi-Regeneron. Satia has served on the following task force committees: Chronic Cough (ERS), Asthma Diagnosis and Management (ERS), NEUROCOUGH (ERS CRC), and the CTS Chronic Cough working group.
A version of this article appeared on Medscape.com.
Lingering postinfectious cough has been a concern across Canada this winter. , according to an overview published on February 12 in the Canadian Medical Association Journal
“It’s something a lot of patients are worried about: That lingering cough after a common cold or flu,” lead author Kevin Liang, MD, of the Department of Family Medicine at The University of British Columbia in Vancouver, British Columbia, Canada, told this news organization. He added that some studies show that as much as a quarter of adult patients have this complaint.
Dr. Liang and his colleagues emphasized that the diagnosis of postinfectious cough is one of exclusion. It relies on the absence of concerning physical examination findings and other “subacute cough mimics” such as asthma, chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease, or use of angiotensin-converting enzyme inhibitors.
“Pertussis should be considered in patients with a paroxysmal cough, post-tussive vomiting, and inspiratory whoop,” they added. Coughs that persist beyond 8 weeks warrant further workup such as a pulmonary function test to rule out asthma or COPD. Coughs accompanied by hemoptysis, systemic symptoms, dysphagia, excessive dyspnea, or hoarseness also warrant further workup, they added. And patients with a history of smoking or recurrent pneumonia should be followed more closely.
In the absence of red flags, Dr. Liang and coauthors advised that there is no evidence supporting pharmacologic treatment, “which is associated with harms,” such as medication adverse effects, cost, strain on the medical supply chain, and the fact that pressurized metered-dose inhalers emit powerful greenhouse gases. “A lot of patients come in looking for solutions, but really, all the evidence says the over-the-counter cough syrup just doesn’t work. Or I see clinicians prescribing inhalers or different medication that can cost hundreds of dollars, and their efficacy, at least from the literature, shows that there’s really no improvement. Time and patience are the two keys to solving this,” Dr. Liang told this news organization.
Moreover, there is a distinct absence of guidelines on this topic. The College of Family Physicians of Canada’s recent literature review cited limited data supporting a trial of inhaled corticosteroids, a bronchodilator such as ipratropium-salbutamol, or an intranasal steroid if postnasal drip is suspected. However, “there’s a high risk of bias in the study they cite from using the short-acting bronchodilators, and what it ultimately says is that in most cases, this is self-resolving by around the 20-day mark,” said Dr. Liang. “Our advice is just to err on the side of caution and just provide that information piece to the patient.”
‘Significant Nuance’
Imran Satia, MD, assistant professor of respirology at McMaster University in Hamilton, Ontario, Canada, agreed that “most people who get a viral or bacterial upper or lower respiratory tract infection will get better with time, and there is very little evidence that giving steroids, antibiotics, or cough suppressants is better than waiting it out.” There is “significant nuance” in how to manage this situation, however.
“In some patients with underlying lung disease like asthma or COPD, increasing the frequency of regular inhaled steroids, bronchodilators, oral steroids, antibiotics, and chest imaging with breathing tests may be clinically warranted, and many physicians will do this,” he told this news organization. “In some patients with refractory chronic cough, there is no underlying identifiable disease, despite completing the necessary investigations. Or coughing persists despite trials of treatment for lung diseases, nasal diseases, and stomach reflux disease. This is commonly described as cough hypersensitivity syndrome, for which therapies targeting the neuronal pathways that control coughing are needed.”
Physicians should occasionally consider trying a temporary course of a short-acting bronchodilator inhaler, said Nicholas Vozoris, MD, assistant professor and clinician investigator in respirology at the University of Toronto, Toronto, Ontario, Canada. “I think that would be a reasonable first step in a case of really bad postinfectious cough,” he told this news organization. “But in general, drug treatments are not indicated.”
Environmental Concerns
Yet some things should raise clinicians’ suspicion of more complex issues.
“A pattern of recurrent colds or bronchitis with protracted coughing afterward raises strong suspicion for asthma, which can present as repeated, prolonged respiratory exacerbations,” he said. “Unless asthma is treated with appropriate inhaler therapy on a regular basis, it will unlikely come under control.”
Dr. Vozoris added that the environmental concerns over the use of metered dose inhalers (MDIs) are minimal compared with the other sources of pollution and the risks for undertreatment. “The authors are overplaying the environmental impact of MDI, in my opinion,” he said. “Physicians already have to deal with the challenging issue of suboptimal patient adherence to inhalers, and I fear that such comments may further drive that up. Furthermore, there is also an environmental footprint with not using inhalers, as patients can then experience suboptimally controlled lung disease as a result — and then present to the ER and get admitted to hospital for exacerbations of disease, where more resources and medications are used up.”
“In addition, in patients who are immunocompromised, protracted coughing after what was thought to be a cold may be associated with an “atypical” respiratory infection, such as tuberculosis, that will require special medical treatment,” Dr. Vozoris concluded.
No funding for the review of postinfectious cough was reported. Dr. Liang and Dr. Vozoris disclosed no competing interests. Dr. Satia reported receiving funding from the ERS Respire 3 Fellowship Award, BMA James Trust Award, North-West Lung Centre Charity (Manchester), NIHR CRF Manchester, Merck MSD, AstraZeneca, and GSK. Dr. Satia also has received consulting fees from Merck MSD, Genentech, and Respiplus; as well as speaker fees from AstraZeneca, GSK, Merck MSD, Sanofi-Regeneron. Satia has served on the following task force committees: Chronic Cough (ERS), Asthma Diagnosis and Management (ERS), NEUROCOUGH (ERS CRC), and the CTS Chronic Cough working group.
A version of this article appeared on Medscape.com.
FROM THE CANADIAN MEDICAL ASSOCIATION JOURNAL
Pretreatment Lab Testing for Chronic Skin Diseases Diverges From Guidelines
in a national commercial insurance claims database.
Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.
“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.
“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.
In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.
The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.
A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.
The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.
Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.
The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.
However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.
“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.
“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”
“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.
Resist Routine Testing
The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.
The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.
However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.
Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.
The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.
Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.
Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.
Dr. Friedman had no relevant financial conflicts to disclose.
A version of this article appeared on Medscape.com.
in a national commercial insurance claims database.
Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.
“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.
“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.
In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.
The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.
A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.
The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.
Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.
The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.
However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.
“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.
“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”
“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.
Resist Routine Testing
The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.
The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.
However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.
Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.
The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.
Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.
Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.
Dr. Friedman had no relevant financial conflicts to disclose.
A version of this article appeared on Medscape.com.
in a national commercial insurance claims database.
Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.
“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.
“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.
In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.
The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.
A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.
The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.
Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.
The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.
However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.
“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.
“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”
“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.
Resist Routine Testing
The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.
The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.
However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.
Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.
The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.
Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.
Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.
Dr. Friedman had no relevant financial conflicts to disclose.
A version of this article appeared on Medscape.com.
FROM JAMA DERMATOLOGY
5 Things to Know About the Future of Obesity Medicine
As more and more treatments for obesity become available, what does the future hold for these patients? Here are five things that clinicians need to know.
1. Public health officials will prioritize dietary quality over quantity.
Dietitians, healthcare providers, and scientists are already prioritizing the quality of calories, and now policymakers are aligning with this goal, with calls for more research on ultraprocessed foods (UPFs) to answer the key question, “Why do UPFs cause people to eat 500 more calories per day compared with unprocessed foods?” The food industry has taken notice of the potential “Ozempic effect” associated with reduced spending on groceries and is responding with product lines “designed to complement” glucagon-like peptide-1 receptor agonists (GLP-1 RAs) while simultaneously lobbying against any UPF reform. However, with emerging data on how sugar taxes may reduce sales and Congress honing in on the diabetes epidemic, we are hopeful that change is coming in 2024.
2. Antiobesity medications will target fat loss instead of weight loss.
The focus on weight has been long-standing, but with highly effective medications like tirzepatide causing about 20% weight loss, attention is shifting to body composition — namely, how do we optimize fat loss while preserving muscle? We are seeing this transition in the research community. Bimagrumab, for example, a once-monthly injection that increases muscle mass and decreases fat mass, is being tested in a phase 3 clinical trial alongside semaglutide. Agents initially designed for spinal muscular atrophy, like apitegromab and taldefgrobep alfa, are being repurposed for obesity. Watch for results of these phase 2 trials in 2024.
3. Increasing energy expenditure is the holy grail of obesity research.
The success of GLP-1 RAs, and the even greater success of dual- and triple-target agents like tirzepatide and retatrutide, tells us that obesity is, indeed, a hormone problem. These medications primarily cause weight loss by suppressing appetite and reducing caloric intake. As scientists develop more therapeutics to normalize appetite regulation, attention will shift to optimizing energy expenditure. Researchers are already investigating brown fat, mitochondrial uncouplers, and skeletal muscle metabolism, but no agent thus far has been proven to be both safe and effective in increasing energy expenditure. Of these, keep an eye on clinical trials involving brown fat and the excitement over the anti-inflammatory cytokine growth differentiating factor 15 (GDF15).
4. Chronic disease without chronic medications.
Obesity is a chronic disease, just like hypertension or diabetes. Similarly, medications that treat chronic diseases are expected to be taken long-term because discontinuation often results in disease recurrence. However, obesity research is getting closer and closer to options that require less frequent administration. Bimagrumab, for example, is a once-monthly injection. In endocrinology, the premier example is osteoporosis: Osteoporosis can be treated with just 3 years of an annual injection and never require treatment again. In obesity, anticipate more basic science discoveries aimed at developing safe and specific treatments that are truly disease-modifying — ones that reverse appetitive dysregulation, reduce proinflammatory adiposity, and optimize anabolic metabolism.
5. Barriers to access are barriers to progress.
The biggest challenge to obesity treatment today is access: drug shortages, medication costs, and lack of obesity medicine providers. Shortages of medications like semaglutide 2.4 mg are being driven by high “demand”; in other words, manufacturers failed to anticipate the massive interest in antiobesity medications.
Medicare and most state Medicaid programs don’t cover these medications; commercial payers are refusing, reversing, or limiting coverage. An out-of-pocket monthly cost over $1000 limits affordability for the majority of Americans.
Seeking care from an obesity medicine doctor is a challenge as well. Over 40% of US adults have obesity, but less than 1% of doctors are certified in obesity medicine. Meanwhile, private equity is eager to address the lack of access through compounding pharmacies, medispas, or telemedicine services, but the quality of care varies greatly. Some companies purposely avoid the term “patient,” preferring ethics-free labels like “consumers” or “members.”
The $100 billion–dollar weight loss industry unfortunately has created financial incentives that drive obesity commerce over obesity care. Because of these barriers, the epidemic of obesity, with a prevalence projected to be 50% by 2030, will not be solved or slowed despite the scientific progress in obesity treatment. A single silver lining exists among policymakers who are aiming to correct our costly sick-care system in steps, starting with pharmacy benefit manager reform. Five of these bills are the ones to track in 2024: Pharmacy Benefit Manager Reform Act, Pharmacy Benefits Manager Accountability Act, Pharmacy Benefit Manager Sunshine and Accountability Act, Pharmacy Benefit Manager Transparency Act of 2023, and Lower Costs, More Transparency Act.
I believe that these five things will have the most impact on the treatment of our patients with obesity. Stay tuned throughout the year as I share updates in obesity research, pharmacotherapy, and public policy.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties with Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
As more and more treatments for obesity become available, what does the future hold for these patients? Here are five things that clinicians need to know.
1. Public health officials will prioritize dietary quality over quantity.
Dietitians, healthcare providers, and scientists are already prioritizing the quality of calories, and now policymakers are aligning with this goal, with calls for more research on ultraprocessed foods (UPFs) to answer the key question, “Why do UPFs cause people to eat 500 more calories per day compared with unprocessed foods?” The food industry has taken notice of the potential “Ozempic effect” associated with reduced spending on groceries and is responding with product lines “designed to complement” glucagon-like peptide-1 receptor agonists (GLP-1 RAs) while simultaneously lobbying against any UPF reform. However, with emerging data on how sugar taxes may reduce sales and Congress honing in on the diabetes epidemic, we are hopeful that change is coming in 2024.
2. Antiobesity medications will target fat loss instead of weight loss.
The focus on weight has been long-standing, but with highly effective medications like tirzepatide causing about 20% weight loss, attention is shifting to body composition — namely, how do we optimize fat loss while preserving muscle? We are seeing this transition in the research community. Bimagrumab, for example, a once-monthly injection that increases muscle mass and decreases fat mass, is being tested in a phase 3 clinical trial alongside semaglutide. Agents initially designed for spinal muscular atrophy, like apitegromab and taldefgrobep alfa, are being repurposed for obesity. Watch for results of these phase 2 trials in 2024.
3. Increasing energy expenditure is the holy grail of obesity research.
The success of GLP-1 RAs, and the even greater success of dual- and triple-target agents like tirzepatide and retatrutide, tells us that obesity is, indeed, a hormone problem. These medications primarily cause weight loss by suppressing appetite and reducing caloric intake. As scientists develop more therapeutics to normalize appetite regulation, attention will shift to optimizing energy expenditure. Researchers are already investigating brown fat, mitochondrial uncouplers, and skeletal muscle metabolism, but no agent thus far has been proven to be both safe and effective in increasing energy expenditure. Of these, keep an eye on clinical trials involving brown fat and the excitement over the anti-inflammatory cytokine growth differentiating factor 15 (GDF15).
4. Chronic disease without chronic medications.
Obesity is a chronic disease, just like hypertension or diabetes. Similarly, medications that treat chronic diseases are expected to be taken long-term because discontinuation often results in disease recurrence. However, obesity research is getting closer and closer to options that require less frequent administration. Bimagrumab, for example, is a once-monthly injection. In endocrinology, the premier example is osteoporosis: Osteoporosis can be treated with just 3 years of an annual injection and never require treatment again. In obesity, anticipate more basic science discoveries aimed at developing safe and specific treatments that are truly disease-modifying — ones that reverse appetitive dysregulation, reduce proinflammatory adiposity, and optimize anabolic metabolism.
5. Barriers to access are barriers to progress.
The biggest challenge to obesity treatment today is access: drug shortages, medication costs, and lack of obesity medicine providers. Shortages of medications like semaglutide 2.4 mg are being driven by high “demand”; in other words, manufacturers failed to anticipate the massive interest in antiobesity medications.
Medicare and most state Medicaid programs don’t cover these medications; commercial payers are refusing, reversing, or limiting coverage. An out-of-pocket monthly cost over $1000 limits affordability for the majority of Americans.
Seeking care from an obesity medicine doctor is a challenge as well. Over 40% of US adults have obesity, but less than 1% of doctors are certified in obesity medicine. Meanwhile, private equity is eager to address the lack of access through compounding pharmacies, medispas, or telemedicine services, but the quality of care varies greatly. Some companies purposely avoid the term “patient,” preferring ethics-free labels like “consumers” or “members.”
The $100 billion–dollar weight loss industry unfortunately has created financial incentives that drive obesity commerce over obesity care. Because of these barriers, the epidemic of obesity, with a prevalence projected to be 50% by 2030, will not be solved or slowed despite the scientific progress in obesity treatment. A single silver lining exists among policymakers who are aiming to correct our costly sick-care system in steps, starting with pharmacy benefit manager reform. Five of these bills are the ones to track in 2024: Pharmacy Benefit Manager Reform Act, Pharmacy Benefits Manager Accountability Act, Pharmacy Benefit Manager Sunshine and Accountability Act, Pharmacy Benefit Manager Transparency Act of 2023, and Lower Costs, More Transparency Act.
I believe that these five things will have the most impact on the treatment of our patients with obesity. Stay tuned throughout the year as I share updates in obesity research, pharmacotherapy, and public policy.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties with Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
As more and more treatments for obesity become available, what does the future hold for these patients? Here are five things that clinicians need to know.
1. Public health officials will prioritize dietary quality over quantity.
Dietitians, healthcare providers, and scientists are already prioritizing the quality of calories, and now policymakers are aligning with this goal, with calls for more research on ultraprocessed foods (UPFs) to answer the key question, “Why do UPFs cause people to eat 500 more calories per day compared with unprocessed foods?” The food industry has taken notice of the potential “Ozempic effect” associated with reduced spending on groceries and is responding with product lines “designed to complement” glucagon-like peptide-1 receptor agonists (GLP-1 RAs) while simultaneously lobbying against any UPF reform. However, with emerging data on how sugar taxes may reduce sales and Congress honing in on the diabetes epidemic, we are hopeful that change is coming in 2024.
2. Antiobesity medications will target fat loss instead of weight loss.
The focus on weight has been long-standing, but with highly effective medications like tirzepatide causing about 20% weight loss, attention is shifting to body composition — namely, how do we optimize fat loss while preserving muscle? We are seeing this transition in the research community. Bimagrumab, for example, a once-monthly injection that increases muscle mass and decreases fat mass, is being tested in a phase 3 clinical trial alongside semaglutide. Agents initially designed for spinal muscular atrophy, like apitegromab and taldefgrobep alfa, are being repurposed for obesity. Watch for results of these phase 2 trials in 2024.
3. Increasing energy expenditure is the holy grail of obesity research.
The success of GLP-1 RAs, and the even greater success of dual- and triple-target agents like tirzepatide and retatrutide, tells us that obesity is, indeed, a hormone problem. These medications primarily cause weight loss by suppressing appetite and reducing caloric intake. As scientists develop more therapeutics to normalize appetite regulation, attention will shift to optimizing energy expenditure. Researchers are already investigating brown fat, mitochondrial uncouplers, and skeletal muscle metabolism, but no agent thus far has been proven to be both safe and effective in increasing energy expenditure. Of these, keep an eye on clinical trials involving brown fat and the excitement over the anti-inflammatory cytokine growth differentiating factor 15 (GDF15).
4. Chronic disease without chronic medications.
Obesity is a chronic disease, just like hypertension or diabetes. Similarly, medications that treat chronic diseases are expected to be taken long-term because discontinuation often results in disease recurrence. However, obesity research is getting closer and closer to options that require less frequent administration. Bimagrumab, for example, is a once-monthly injection. In endocrinology, the premier example is osteoporosis: Osteoporosis can be treated with just 3 years of an annual injection and never require treatment again. In obesity, anticipate more basic science discoveries aimed at developing safe and specific treatments that are truly disease-modifying — ones that reverse appetitive dysregulation, reduce proinflammatory adiposity, and optimize anabolic metabolism.
5. Barriers to access are barriers to progress.
The biggest challenge to obesity treatment today is access: drug shortages, medication costs, and lack of obesity medicine providers. Shortages of medications like semaglutide 2.4 mg are being driven by high “demand”; in other words, manufacturers failed to anticipate the massive interest in antiobesity medications.
Medicare and most state Medicaid programs don’t cover these medications; commercial payers are refusing, reversing, or limiting coverage. An out-of-pocket monthly cost over $1000 limits affordability for the majority of Americans.
Seeking care from an obesity medicine doctor is a challenge as well. Over 40% of US adults have obesity, but less than 1% of doctors are certified in obesity medicine. Meanwhile, private equity is eager to address the lack of access through compounding pharmacies, medispas, or telemedicine services, but the quality of care varies greatly. Some companies purposely avoid the term “patient,” preferring ethics-free labels like “consumers” or “members.”
The $100 billion–dollar weight loss industry unfortunately has created financial incentives that drive obesity commerce over obesity care. Because of these barriers, the epidemic of obesity, with a prevalence projected to be 50% by 2030, will not be solved or slowed despite the scientific progress in obesity treatment. A single silver lining exists among policymakers who are aiming to correct our costly sick-care system in steps, starting with pharmacy benefit manager reform. Five of these bills are the ones to track in 2024: Pharmacy Benefit Manager Reform Act, Pharmacy Benefits Manager Accountability Act, Pharmacy Benefit Manager Sunshine and Accountability Act, Pharmacy Benefit Manager Transparency Act of 2023, and Lower Costs, More Transparency Act.
I believe that these five things will have the most impact on the treatment of our patients with obesity. Stay tuned throughout the year as I share updates in obesity research, pharmacotherapy, and public policy.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties with Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
AGA Tech Summit Focuses on Accelerating Innovation
The AGA Tech Summit is building on the success of past summits and moving in a new direction. The reimagined summit will accelerate innovation by bringing together MedTech startups, innovators, investors and leaders in the field.
“It’s a new world out there. The Tech Summit now reflects the new direction AGA is taking in innovation,” said Lawrence R. Kosinski, MD, AGA at-large councilor for development and growth. “We want to help GI innovators successfully navigate the innovation lifecycle from start to finish and bring new technologies to market.”
The Tech Summit will take place April 11-12 in Chicago at MATTER, located at the Merchandise Mart. MATTER supports healthcare startups at all stages of growth and brings together industry executives, entrepreneurs, and investors to accelerate innovation, advance care and improve lives.
Highlights of the Tech Summit include:
- Keynote addresses from leaders in the field of GI innovation.
- Panel discussions with VC strategists.
- The Shark Tank Pitch Competition featuring emerging GI technologies.
- Multiple opportunities to network innovators, investors and leaders in the field.
- One-on-one consultations with VCs.
.
The AGA Tech Summit is building on the success of past summits and moving in a new direction. The reimagined summit will accelerate innovation by bringing together MedTech startups, innovators, investors and leaders in the field.
“It’s a new world out there. The Tech Summit now reflects the new direction AGA is taking in innovation,” said Lawrence R. Kosinski, MD, AGA at-large councilor for development and growth. “We want to help GI innovators successfully navigate the innovation lifecycle from start to finish and bring new technologies to market.”
The Tech Summit will take place April 11-12 in Chicago at MATTER, located at the Merchandise Mart. MATTER supports healthcare startups at all stages of growth and brings together industry executives, entrepreneurs, and investors to accelerate innovation, advance care and improve lives.
Highlights of the Tech Summit include:
- Keynote addresses from leaders in the field of GI innovation.
- Panel discussions with VC strategists.
- The Shark Tank Pitch Competition featuring emerging GI technologies.
- Multiple opportunities to network innovators, investors and leaders in the field.
- One-on-one consultations with VCs.
.
The AGA Tech Summit is building on the success of past summits and moving in a new direction. The reimagined summit will accelerate innovation by bringing together MedTech startups, innovators, investors and leaders in the field.
“It’s a new world out there. The Tech Summit now reflects the new direction AGA is taking in innovation,” said Lawrence R. Kosinski, MD, AGA at-large councilor for development and growth. “We want to help GI innovators successfully navigate the innovation lifecycle from start to finish and bring new technologies to market.”
The Tech Summit will take place April 11-12 in Chicago at MATTER, located at the Merchandise Mart. MATTER supports healthcare startups at all stages of growth and brings together industry executives, entrepreneurs, and investors to accelerate innovation, advance care and improve lives.
Highlights of the Tech Summit include:
- Keynote addresses from leaders in the field of GI innovation.
- Panel discussions with VC strategists.
- The Shark Tank Pitch Competition featuring emerging GI technologies.
- Multiple opportunities to network innovators, investors and leaders in the field.
- One-on-one consultations with VCs.
.
Insulin and Oral Diabetes Drugs Are Similarly Effective for Gestational Diabetes
NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.
After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).
Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.
In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.
The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.
The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.
The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.
The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.
Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.
Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).
Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.
Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.
Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).
Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
Data Support Orals as Effective Gestational Diabetes Option
“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.
Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.
The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.
Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.
A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.
Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.
The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.
After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).
Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.
In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.
The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.
The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.
The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.
The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.
Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.
Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).
Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.
Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.
Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).
Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
Data Support Orals as Effective Gestational Diabetes Option
“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.
Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.
The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.
Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.
A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.
Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.
The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.
After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).
Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.
In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.
The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.
The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.
The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.
The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.
Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.
Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).
Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.
Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.
Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).
Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
Data Support Orals as Effective Gestational Diabetes Option
“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.
Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.
The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.
Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.
A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.
Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.
The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.
FROM THE PREGNANCY MEETING
Prevalence of Risk Factors Impacting Oral Janus Kinase Inhibitor Treatment in Atopic Dermatitis
Key clinical point: Risk factors affecting oral Janus kinase inhibitor (JAKi) treatment were prevalent among adult patients with atopic dermatitis (AD), especially older individuals, thus necessitating careful risk assessment among patients before JAKi therapy initiation.
Major finding: Nearly half (49.5%) of the patients with AD at some point had at least one risk factor that could affect JAKi treatment and most (60.3%) patients age ≥ 65 years had at least three risk factors. The recorded non-modifiable risk factors included cancer (5.6%), smoking history (15.6%), age ≥ 65 years (12.4%), and major adverse cardiovascular events (2.6%).
Study details: This cross-sectional study included adult patients with AD from the Danish national registers (n = 18,618) and Danish Skin Cohort (n = 3573).
Disclosures: This study did not disclose the source of funding. Several authors declared receiving research support, lecture honoraria, or consulting honoraria from or serving as speakers or advisory board members for various organizations.
Source: Vittrup I, Thein D, Thomsen SF, Egeberg A, Thyssen JP. Risk factors that impact treatment with oral Janus kinase inhibitors among adult patients with atopic dermatitis: A nationwide registry study. Acta Derm Venereol. 2024 (Jan 22). doi: 10.2340/actadv.v104.18638 Source
Key clinical point: Risk factors affecting oral Janus kinase inhibitor (JAKi) treatment were prevalent among adult patients with atopic dermatitis (AD), especially older individuals, thus necessitating careful risk assessment among patients before JAKi therapy initiation.
Major finding: Nearly half (49.5%) of the patients with AD at some point had at least one risk factor that could affect JAKi treatment and most (60.3%) patients age ≥ 65 years had at least three risk factors. The recorded non-modifiable risk factors included cancer (5.6%), smoking history (15.6%), age ≥ 65 years (12.4%), and major adverse cardiovascular events (2.6%).
Study details: This cross-sectional study included adult patients with AD from the Danish national registers (n = 18,618) and Danish Skin Cohort (n = 3573).
Disclosures: This study did not disclose the source of funding. Several authors declared receiving research support, lecture honoraria, or consulting honoraria from or serving as speakers or advisory board members for various organizations.
Source: Vittrup I, Thein D, Thomsen SF, Egeberg A, Thyssen JP. Risk factors that impact treatment with oral Janus kinase inhibitors among adult patients with atopic dermatitis: A nationwide registry study. Acta Derm Venereol. 2024 (Jan 22). doi: 10.2340/actadv.v104.18638 Source
Key clinical point: Risk factors affecting oral Janus kinase inhibitor (JAKi) treatment were prevalent among adult patients with atopic dermatitis (AD), especially older individuals, thus necessitating careful risk assessment among patients before JAKi therapy initiation.
Major finding: Nearly half (49.5%) of the patients with AD at some point had at least one risk factor that could affect JAKi treatment and most (60.3%) patients age ≥ 65 years had at least three risk factors. The recorded non-modifiable risk factors included cancer (5.6%), smoking history (15.6%), age ≥ 65 years (12.4%), and major adverse cardiovascular events (2.6%).
Study details: This cross-sectional study included adult patients with AD from the Danish national registers (n = 18,618) and Danish Skin Cohort (n = 3573).
Disclosures: This study did not disclose the source of funding. Several authors declared receiving research support, lecture honoraria, or consulting honoraria from or serving as speakers or advisory board members for various organizations.
Source: Vittrup I, Thein D, Thomsen SF, Egeberg A, Thyssen JP. Risk factors that impact treatment with oral Janus kinase inhibitors among adult patients with atopic dermatitis: A nationwide registry study. Acta Derm Venereol. 2024 (Jan 22). doi: 10.2340/actadv.v104.18638 Source
Dupilumab Efficacy in Atopic Dermatitis Is Not Influenced by Pathogenic Filaggrin Variants
Key clinical point: Pathogenic filaggrin (FLG) variants do not affect the effectiveness of dupilumab treatment in patients with atopic dermatitis (AD).
Major finding: No clinically relevant differences were observed in the Eczema Area and Severity Index, Investigator Global Assessment, Numeric Rating Scale for pruritus, and total Patient Oriented Eczema Measure (POEM) scores between patients with and without pathogenic FLG variants at week 16 or 52. However, patients with bi-allelic pathogenic variants vs wild-type alleles had significantly higher POEM dryness scores at week 16 (P = .002) and week 52 (P = .016).
Study details: This prospective observational study included 285 adult patients with AD from the Dutch BioDay Registry who had received dupilumab for 16 weeks or more and underwent genomic variant analysis for FLG.
Disclosures: This study did not receive any funding. Some authors declared being consultants, advisory board members, or speakers for or having other ties with various organizations.
Source: Clabbers J, Boesjes C, Spekhorst L, et al. Influence of pathogenic filaggrin variants on dupilumab treatment in atopic dermatitis. J Allergy Clin Immunol. 2024 (Jan 22). doi: 10.1016/j.jaci.2023.12.027 Source
Key clinical point: Pathogenic filaggrin (FLG) variants do not affect the effectiveness of dupilumab treatment in patients with atopic dermatitis (AD).
Major finding: No clinically relevant differences were observed in the Eczema Area and Severity Index, Investigator Global Assessment, Numeric Rating Scale for pruritus, and total Patient Oriented Eczema Measure (POEM) scores between patients with and without pathogenic FLG variants at week 16 or 52. However, patients with bi-allelic pathogenic variants vs wild-type alleles had significantly higher POEM dryness scores at week 16 (P = .002) and week 52 (P = .016).
Study details: This prospective observational study included 285 adult patients with AD from the Dutch BioDay Registry who had received dupilumab for 16 weeks or more and underwent genomic variant analysis for FLG.
Disclosures: This study did not receive any funding. Some authors declared being consultants, advisory board members, or speakers for or having other ties with various organizations.
Source: Clabbers J, Boesjes C, Spekhorst L, et al. Influence of pathogenic filaggrin variants on dupilumab treatment in atopic dermatitis. J Allergy Clin Immunol. 2024 (Jan 22). doi: 10.1016/j.jaci.2023.12.027 Source
Key clinical point: Pathogenic filaggrin (FLG) variants do not affect the effectiveness of dupilumab treatment in patients with atopic dermatitis (AD).
Major finding: No clinically relevant differences were observed in the Eczema Area and Severity Index, Investigator Global Assessment, Numeric Rating Scale for pruritus, and total Patient Oriented Eczema Measure (POEM) scores between patients with and without pathogenic FLG variants at week 16 or 52. However, patients with bi-allelic pathogenic variants vs wild-type alleles had significantly higher POEM dryness scores at week 16 (P = .002) and week 52 (P = .016).
Study details: This prospective observational study included 285 adult patients with AD from the Dutch BioDay Registry who had received dupilumab for 16 weeks or more and underwent genomic variant analysis for FLG.
Disclosures: This study did not receive any funding. Some authors declared being consultants, advisory board members, or speakers for or having other ties with various organizations.
Source: Clabbers J, Boesjes C, Spekhorst L, et al. Influence of pathogenic filaggrin variants on dupilumab treatment in atopic dermatitis. J Allergy Clin Immunol. 2024 (Jan 22). doi: 10.1016/j.jaci.2023.12.027 Source