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Economic burden of migraine increases with the number of treatment failures
, researchers wrote. Utilization of health care resources and associated costs are greater among patients with three or more treatment failures, compared with patients with fewer treatment failures. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Migraine entails a significant economic burden, including direct costs (e.g., medical costs) and indirect costs (e.g., lost productivity). Information about the burden associated with failed preventive treatments among migraineurs is limited, however. Lawrence C. Newman, MD, director of the division of headache at NYU Langone Health in New York, and colleagues conducted a study to characterize health care resource utilization (HCRU) and its associated costs among migraineurs, stratified by the number of preventive treatment failures.
About one quarter of patients had two treatment failures
Using data from the IBM MarketScan Commercial and Medicare Supplemental database, Dr. Newman and colleagues identified patients who received a new diagnosis of migraine between Jan. 1, 2011, and June 30, 2015. Next, they identified the number of treatment failures during the 2 years following the initial migraine diagnosis. They assessed HCRU and associated costs during the 12 months following an index event. The index was the date of initiation of the second preventive treatment for patients with one treatment failure, the date of initiation of the third treatment for patients with two treatment failures, and the date of initiation of the fourth treatment for patients with three or more treatment failures.
Dr. Newman’s group identified 44,181 patients with incident migraine who had failed preventive treatments. Of this population, 27,112 patients (61.4%) had one treatment failure, 10,583 (24%) had two treatment failures, and 6,486 (14.7%) had three or more treatment failures.
The total medical cost per patient, including emergency room (ER), inpatient (IP), and outpatient (OP) care, increased with increasing number of treatment failures ($10,329 for one, $13,774 for two, and $35,392 for three or more). When the investigators added prescription drug costs, the total health care costs also increased with number of treatment failures ($13,946 for one, $18,685 for two, and $41,864 for three or more).
Similarly, the per-patient annual health care provider visits increased with increasing numbers of treatment failures. The number of ER visits per year was 0.54, 0.69, and 1.02 for patients with one, two, and three or more treatment failures, respectively. The annual number of IP visits was 0.46, 0.59, and 0.97, for patients with one, two, and three or more treatment failures, respectively. OP visits showed a similar trend. The annual number of office visits was 9.47 for patients with one, 11.24 for patients with two, and 14.26 for patients with three or more treatment failures. The annual number of other visits was 13.15 for patients with one, 15.73 for patients with two, and 19.96 for patients with three or more treatment failures.
Guidelines could enable appropriate treatment
Reasons for treatment failure include misdiagnosis of the headache disorder, failure to identify and account for comorbidities, overlooking concurrent acute medication overuse, and inappropriate dose or formulation, said Dr. Newman. “Common pitfalls in prevention that lead to treatment failure include not using evidence-based treatments, starting at too low of a dose and not increasing, starting too high or increasing the dose too quickly, discontinuing the medication before an effect can be seen (before 8 weeks), patient nonadherence, and not establishing realistic expectations.”
Available resources could help clinicians treat migraine effectively. “The American Headache Society (AHS)/AAN preventive guidelines have been retired, yet they offered several levels of effectiveness of pharmacologic treatments that were evidence-based,” said Dr. Newman. “Furthermore, in 2019, the AHS published a consensus statement on integrating new migraine treatments into clinical practice. This statement offered advice about the new anti-CGRP agents, onabotulinum toxin, and neuromodulation devices. I think this is a good starting point for neurologists to be familiar with to choose appropriate therapeutic options for people living with migraine.”
Earlier treatment may reduce patients’ economic burden
The study’s weaknesses included its observational design and its reliance on diagnostic codes, which raised the possibility that comorbidities were inadequately recognized, said Dr. Newman. The reasons that patients changed medications are unknown, and the results are not generalizable to patients aged 65 years or older, he added.
Major strengths of Dr. Newman’s study are its large sample size and wealth of available data, said Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “The multiple subcategories suggest that this was a carefully organized and implemented study,” he added. If any diagnoses of migraine were provided by general practitioners with little knowledge of migraine, this would weaken the study, said Dr. Rapoport, editor-in-chief of Neurology Reviews.
“We can ease the economic burden of migraineurs by improving acute care therapy with better selection and earlier starting of effective preventive therapy,” he continued. “Going for migraine-specific acute care therapy is better than pain medications or other nonspecific therapies. If you do not stop a migraine attack with effective therapy, you increase the odds that the patient will go on to chronic migraine. It is always important to effectively teach doctors and nurses to improve their diagnostic skills and use the optimal acute and preventive therapy.” For their next trial, maximizing an accurate diagnosis and performing a prospective study measuring treatment outcomes will be particularly valuable, Dr. Rapoport concluded.
Dr. Newman’s study was supported by Novartis Pharma in Basel, Switzerland. Together with Amgen, Novartis developed erenumab. Dr. Newman has received compensation from Allergan, Alder, Amgen, Biohaven, Novartis, Teva, Supernus, and Theranica for consulting, serving on a scientific advisory board, speaking, or other activities. He has received compensation from Springer Scientific for editorial services.
SOURCE: Newman L et al. AAN 2020, Abstract S47.009.
, researchers wrote. Utilization of health care resources and associated costs are greater among patients with three or more treatment failures, compared with patients with fewer treatment failures. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Migraine entails a significant economic burden, including direct costs (e.g., medical costs) and indirect costs (e.g., lost productivity). Information about the burden associated with failed preventive treatments among migraineurs is limited, however. Lawrence C. Newman, MD, director of the division of headache at NYU Langone Health in New York, and colleagues conducted a study to characterize health care resource utilization (HCRU) and its associated costs among migraineurs, stratified by the number of preventive treatment failures.
About one quarter of patients had two treatment failures
Using data from the IBM MarketScan Commercial and Medicare Supplemental database, Dr. Newman and colleagues identified patients who received a new diagnosis of migraine between Jan. 1, 2011, and June 30, 2015. Next, they identified the number of treatment failures during the 2 years following the initial migraine diagnosis. They assessed HCRU and associated costs during the 12 months following an index event. The index was the date of initiation of the second preventive treatment for patients with one treatment failure, the date of initiation of the third treatment for patients with two treatment failures, and the date of initiation of the fourth treatment for patients with three or more treatment failures.
Dr. Newman’s group identified 44,181 patients with incident migraine who had failed preventive treatments. Of this population, 27,112 patients (61.4%) had one treatment failure, 10,583 (24%) had two treatment failures, and 6,486 (14.7%) had three or more treatment failures.
The total medical cost per patient, including emergency room (ER), inpatient (IP), and outpatient (OP) care, increased with increasing number of treatment failures ($10,329 for one, $13,774 for two, and $35,392 for three or more). When the investigators added prescription drug costs, the total health care costs also increased with number of treatment failures ($13,946 for one, $18,685 for two, and $41,864 for three or more).
Similarly, the per-patient annual health care provider visits increased with increasing numbers of treatment failures. The number of ER visits per year was 0.54, 0.69, and 1.02 for patients with one, two, and three or more treatment failures, respectively. The annual number of IP visits was 0.46, 0.59, and 0.97, for patients with one, two, and three or more treatment failures, respectively. OP visits showed a similar trend. The annual number of office visits was 9.47 for patients with one, 11.24 for patients with two, and 14.26 for patients with three or more treatment failures. The annual number of other visits was 13.15 for patients with one, 15.73 for patients with two, and 19.96 for patients with three or more treatment failures.
Guidelines could enable appropriate treatment
Reasons for treatment failure include misdiagnosis of the headache disorder, failure to identify and account for comorbidities, overlooking concurrent acute medication overuse, and inappropriate dose or formulation, said Dr. Newman. “Common pitfalls in prevention that lead to treatment failure include not using evidence-based treatments, starting at too low of a dose and not increasing, starting too high or increasing the dose too quickly, discontinuing the medication before an effect can be seen (before 8 weeks), patient nonadherence, and not establishing realistic expectations.”
Available resources could help clinicians treat migraine effectively. “The American Headache Society (AHS)/AAN preventive guidelines have been retired, yet they offered several levels of effectiveness of pharmacologic treatments that were evidence-based,” said Dr. Newman. “Furthermore, in 2019, the AHS published a consensus statement on integrating new migraine treatments into clinical practice. This statement offered advice about the new anti-CGRP agents, onabotulinum toxin, and neuromodulation devices. I think this is a good starting point for neurologists to be familiar with to choose appropriate therapeutic options for people living with migraine.”
Earlier treatment may reduce patients’ economic burden
The study’s weaknesses included its observational design and its reliance on diagnostic codes, which raised the possibility that comorbidities were inadequately recognized, said Dr. Newman. The reasons that patients changed medications are unknown, and the results are not generalizable to patients aged 65 years or older, he added.
Major strengths of Dr. Newman’s study are its large sample size and wealth of available data, said Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “The multiple subcategories suggest that this was a carefully organized and implemented study,” he added. If any diagnoses of migraine were provided by general practitioners with little knowledge of migraine, this would weaken the study, said Dr. Rapoport, editor-in-chief of Neurology Reviews.
“We can ease the economic burden of migraineurs by improving acute care therapy with better selection and earlier starting of effective preventive therapy,” he continued. “Going for migraine-specific acute care therapy is better than pain medications or other nonspecific therapies. If you do not stop a migraine attack with effective therapy, you increase the odds that the patient will go on to chronic migraine. It is always important to effectively teach doctors and nurses to improve their diagnostic skills and use the optimal acute and preventive therapy.” For their next trial, maximizing an accurate diagnosis and performing a prospective study measuring treatment outcomes will be particularly valuable, Dr. Rapoport concluded.
Dr. Newman’s study was supported by Novartis Pharma in Basel, Switzerland. Together with Amgen, Novartis developed erenumab. Dr. Newman has received compensation from Allergan, Alder, Amgen, Biohaven, Novartis, Teva, Supernus, and Theranica for consulting, serving on a scientific advisory board, speaking, or other activities. He has received compensation from Springer Scientific for editorial services.
SOURCE: Newman L et al. AAN 2020, Abstract S47.009.
, researchers wrote. Utilization of health care resources and associated costs are greater among patients with three or more treatment failures, compared with patients with fewer treatment failures. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Migraine entails a significant economic burden, including direct costs (e.g., medical costs) and indirect costs (e.g., lost productivity). Information about the burden associated with failed preventive treatments among migraineurs is limited, however. Lawrence C. Newman, MD, director of the division of headache at NYU Langone Health in New York, and colleagues conducted a study to characterize health care resource utilization (HCRU) and its associated costs among migraineurs, stratified by the number of preventive treatment failures.
About one quarter of patients had two treatment failures
Using data from the IBM MarketScan Commercial and Medicare Supplemental database, Dr. Newman and colleagues identified patients who received a new diagnosis of migraine between Jan. 1, 2011, and June 30, 2015. Next, they identified the number of treatment failures during the 2 years following the initial migraine diagnosis. They assessed HCRU and associated costs during the 12 months following an index event. The index was the date of initiation of the second preventive treatment for patients with one treatment failure, the date of initiation of the third treatment for patients with two treatment failures, and the date of initiation of the fourth treatment for patients with three or more treatment failures.
Dr. Newman’s group identified 44,181 patients with incident migraine who had failed preventive treatments. Of this population, 27,112 patients (61.4%) had one treatment failure, 10,583 (24%) had two treatment failures, and 6,486 (14.7%) had three or more treatment failures.
The total medical cost per patient, including emergency room (ER), inpatient (IP), and outpatient (OP) care, increased with increasing number of treatment failures ($10,329 for one, $13,774 for two, and $35,392 for three or more). When the investigators added prescription drug costs, the total health care costs also increased with number of treatment failures ($13,946 for one, $18,685 for two, and $41,864 for three or more).
Similarly, the per-patient annual health care provider visits increased with increasing numbers of treatment failures. The number of ER visits per year was 0.54, 0.69, and 1.02 for patients with one, two, and three or more treatment failures, respectively. The annual number of IP visits was 0.46, 0.59, and 0.97, for patients with one, two, and three or more treatment failures, respectively. OP visits showed a similar trend. The annual number of office visits was 9.47 for patients with one, 11.24 for patients with two, and 14.26 for patients with three or more treatment failures. The annual number of other visits was 13.15 for patients with one, 15.73 for patients with two, and 19.96 for patients with three or more treatment failures.
Guidelines could enable appropriate treatment
Reasons for treatment failure include misdiagnosis of the headache disorder, failure to identify and account for comorbidities, overlooking concurrent acute medication overuse, and inappropriate dose or formulation, said Dr. Newman. “Common pitfalls in prevention that lead to treatment failure include not using evidence-based treatments, starting at too low of a dose and not increasing, starting too high or increasing the dose too quickly, discontinuing the medication before an effect can be seen (before 8 weeks), patient nonadherence, and not establishing realistic expectations.”
Available resources could help clinicians treat migraine effectively. “The American Headache Society (AHS)/AAN preventive guidelines have been retired, yet they offered several levels of effectiveness of pharmacologic treatments that were evidence-based,” said Dr. Newman. “Furthermore, in 2019, the AHS published a consensus statement on integrating new migraine treatments into clinical practice. This statement offered advice about the new anti-CGRP agents, onabotulinum toxin, and neuromodulation devices. I think this is a good starting point for neurologists to be familiar with to choose appropriate therapeutic options for people living with migraine.”
Earlier treatment may reduce patients’ economic burden
The study’s weaknesses included its observational design and its reliance on diagnostic codes, which raised the possibility that comorbidities were inadequately recognized, said Dr. Newman. The reasons that patients changed medications are unknown, and the results are not generalizable to patients aged 65 years or older, he added.
Major strengths of Dr. Newman’s study are its large sample size and wealth of available data, said Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “The multiple subcategories suggest that this was a carefully organized and implemented study,” he added. If any diagnoses of migraine were provided by general practitioners with little knowledge of migraine, this would weaken the study, said Dr. Rapoport, editor-in-chief of Neurology Reviews.
“We can ease the economic burden of migraineurs by improving acute care therapy with better selection and earlier starting of effective preventive therapy,” he continued. “Going for migraine-specific acute care therapy is better than pain medications or other nonspecific therapies. If you do not stop a migraine attack with effective therapy, you increase the odds that the patient will go on to chronic migraine. It is always important to effectively teach doctors and nurses to improve their diagnostic skills and use the optimal acute and preventive therapy.” For their next trial, maximizing an accurate diagnosis and performing a prospective study measuring treatment outcomes will be particularly valuable, Dr. Rapoport concluded.
Dr. Newman’s study was supported by Novartis Pharma in Basel, Switzerland. Together with Amgen, Novartis developed erenumab. Dr. Newman has received compensation from Allergan, Alder, Amgen, Biohaven, Novartis, Teva, Supernus, and Theranica for consulting, serving on a scientific advisory board, speaking, or other activities. He has received compensation from Springer Scientific for editorial services.
SOURCE: Newman L et al. AAN 2020, Abstract S47.009.
From AAN 2020
Case series suggests biologics, JAK inhibitors safe during pandemic
Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.
“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.
There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.
Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.
Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.
A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.
Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.
Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.
Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).
It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.
Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.
Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.
The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.
As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”
There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.
aotto@mdedge.com
SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.
Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.
“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.
There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.
Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.
Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.
A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.
Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.
Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.
Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).
It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.
Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.
Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.
The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.
As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”
There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.
aotto@mdedge.com
SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.
Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.
“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.
There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.
Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.
Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.
A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.
Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.
Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.
Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).
It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.
Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.
Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.
The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.
As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”
There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.
aotto@mdedge.com
SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
POPCoRN network mobilizes pediatric capacity during pandemic
Med-Peds hospitalists were an organizing force
As U.S. health care systems prepare for inpatient surges linked to hospitalizations of critically ill COVID-19 patients, two hospitalists with med-peds training (combined training in internal medicine and pediatrics) have launched an innovative solution to help facilities deal with the challenge.
The Pediatric Overflow Planning Contingency Response Network (POPCoRN network) has quickly linked almost 400 physicians and other health professionals, including hospitalists, attending physicians, residents, medical students, and nurses. The network wants to help provide more information about how pediatric-focused institutions can safely gear up to admit adult patients in children’s hospitals, in order to offset the predicted demand for hospital beds for patients with COVID-19.
According to the POPCoRN network website (www.popcornetwork.org), the majority of providers who have contacted the network say they have already started or are committed to planning for their pediatric facilities to be used for adult overflow. The Children’s Hospital Association has issued a guidance on this kind of community collaboration for children’s hospitals partnering with adult hospitals in their community and with policy makers.
“We are a network of folks from different institutions, many med-peds–trained hospitalists but quickly growing,” said Leah Ratner, MD, a second-year fellow in the Global Pediatrics Program at Boston Children’s Hospital and cofounder of the POPCoRN network. “We came together to think about how to increase capacity – both in the work force and for actual hospital space – by helping to train pediatric hospitalists and pediatrics-trained nurses to care for adult patients.”
A web-based platform filled with a rapidly expanding list of resources, an active Twitter account, and utilization of Zoom networking software for webinars and working group meetings have facilitated the network’s growth. “Social media has helped us,” Dr. Ratner said. But equally important are personal connections.
“It all started just a few weeks ago,” added cofounder Ashley Jenkins, MD, a med-peds hospital medicine and general academics research fellow in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. “I sent out some emails in mid-March, asking what other people were doing about these issues. Leah and I met as a result of these initial emails. We immediately started connecting with other health systems and it just expanded from there. Once we knew that enough other systems were thinking about it and trying to build capacity, we started pulling the people and information together.”
High-yield one-pagers
A third or more of those on the POPCoRN contact list are also participating as volunteers on its varied working groups, including health system operation groups exploring the needs of three distinct hospital models: freestanding children’s hospitals; community hospitals, which may see small numbers of children; and integrated mixed hospitals, which often means a pediatric hospital or pediatric units located within an adult hospital.
An immediate goal is to develop high-yield informational “one-pagers,” culling essential clinical facts on a variety of topics in adult inpatient medicine that may no longer be familiar to working pediatric hospitalists. These one-pagers, designed with the help of network members with graphic design skills, address topics such as syncope or chest pain or managing exacerbation of COPD in adults. They draw upon existing informational sources, encapsulating practical information tips that can be used at the bedside, including test workups, differential diagnoses, treatment approaches, and other pearls for providers. Drafts are reviewed for content by specialists, and then by pediatricians to make sure the information covers what they need.
Also under development are educational materials for nurses trained in pediatrics, a section for outpatient providers redeployed to triage or telehealth, and information for other team members including occupational, physical, and respiratory therapists. Another section offers critical care lectures for the nonintensivist. A metrics and outcomes working group is looking for ways to evaluate how the network is doing and who is being reached without having to ask frontline providers to fill out surveys.
Dr. Ratner and Dr. Jenkins have created an intentional structure for encouraging mentoring. They also call on their own mentors – Ahmet Uluer, DO, director of Weitzman Family Bridges Adult Transition Program at Boston Children’s Hospital, and Brian Herbst Jr., MD, medical director of the Hospital Medicine Adult Care Service at Cincinnati Children’s – for advice.
Beyond the silos
Pediatric hospitalists may have been doing similar things, working on similar projects, but not necessarily reaching out to each other across a system that tends to promote staying within administrative silos, Dr. Uluer said. “Through our personal contacts in POPCoRN, we’ve been able to reach beyond the silos. This network has worked like medical crowd sourcing, and the founders have been inspirational.”
Dr. Herbst added, “How do we expand bandwidth and safely expand services to take young patients and adults from other hospitals? What other populations do we need to expand to take? This network is a workplace of ideas. It’s amazing to see what has been built in a few weeks and how useful it can be.”
Med-peds hospitalists are an important resource for bridging the two specialties. Their experience with transitioning young adults with long-standing chronic conditions of childhood, who have received most of their care at a children’s hospital before reaching adulthood, offers a helpful model. “We’ve also tried to target junior physicians who could step up into leadership roles and to pull in medical students – who are the backbone of this network through their administrative support,” Dr. Jenkins said.
Marie Pfarr, MD, also a med-peds trained hospital medicine fellow at Cincinnati Children’s, was contacted in March by Dr. Jenkins. “She said they had this brainstorm, and they were getting feedback that it would be helpful to provide educational materials for pediatric providers. Because I have an interest in medical education, she asked if I wanted to help. I was at home struggling with what I could contribute during this crazy time, so I said yes.”
Dr. Pfarr leads POPCoRN’s educational working group, which came up with a list of 50 topics in need of one-pagers and people willing to create them, mostly still under development. The aim for the one-pagers is to offer a good starting point for pediatricians, helping them, for example, to ask the right questions during history and physical exams. “We also want to offer additional resources for those who want to do a deeper dive.”
Dr. Pfarr said she has enjoyed working closely with medical students, who really want to help. “That’s been great to see. We are all working toward the same goal, and we help to keep each other in check. I think there’s a future for this kind of mobilization through collaborations to connect pediatric to adult providers. A lot of good things will come out of the network, which is an example of how folks can talk to each other. It’s very dynamic and changing every day.”
One of those medical students is Chinma Onyewuenyi, finishing her fourth year at Baylor College of Medicine. Scheduled to start a med-peds residency at Geisinger Health on July 1, she had completed all of her rotations and was looking for ways to get involved in the pandemic response while respecting the shelter-in-place order. “I had heard about the network, which was recruiting medical students to play administrative roles for the working groups. I said, ‘If you have anything else you need help with, I have time on my hands.’”
Ms. Onyewuenyi says she fell into the role of a lead administrative volunteer, and her responsibilities grew from there, eventually taking charge of all the medical students’ recruiting, screening, and assignments, freeing up the project’s physician leaders from administrative tasks. “I wanted something active to do to contribute, and I appreciate all that I’m learning. With a master’s degree in public health, I have researched how health care is delivered,” she said.
“This experience has really opened my eyes to what’s required to deliver care, and just the level of collaboration that needs to go on with something like this. Even as a medical student, I felt glad to have an opportunity to contribute beyond the administrative tasks. At meetings, they ask for my opinion.”
Equitable access to resources
Another major focus for the network is promoting health equity – giving pediatric providers and health systems equitable access to information that meets their needs, Dr. Ratner said. “We’ve made a particular effort to reach out to hospitals that are the most vulnerable, including rural hospitals, and to those serving the most vulnerable patients,” she noted. These also include the homeless and refugees.
“We’ve been trying to be mindful of avoiding the sometimes-intimidating power structure that has been traditional in medicine,” Dr. Ratner said. The network’s equity working group is trying to provide content with structural competency and cultural humility. “We’re learning a lot about the ways the health care system is broken,” she added. “We all agree that we have a fragmented health care system, but there are ways to make it less fragmented and learn from each other.”
In the tragedy of the COVID epidemic, there are also unique opportunities to learn to work collaboratively and make the health care system stronger for those in greatest need, Dr. Ratner added. “What we hope is that our network becomes an example of that, even as it is moving so quickly.”
Audrey Uong, MD, an attending physician in the division of hospital medicine at Children’s Hospital at Montefiore Medical Center in New York, connected with POPCoRN for an educational presentation reviewing resuscitation in adult patients. She wanted to talk with peers about what’s going on, so as not to feel alone in her practice. She has also found the network’s website useful for identifying educational resources.
“As pediatricians, we have been asked to care for adult patients. One of our units has been admitting mostly patients under age 30, and we are accepting older patients in another unit on the pediatric wing.” This kind of thing is also happening in a lot of other places, Dr. Uong said. Keeping up with these changes in her own practice has been challenging.
She tries to take one day at a time. “Everyone at this institution feels the same – that we’re locked in on meeting the need. Even our child life specialists, when they’re not working with younger patients, have created this amazing support room for staff, with snacks and soothing music. There’s been a lot of attention paid to making us feel supported in this work.”
Med-Peds hospitalists were an organizing force
Med-Peds hospitalists were an organizing force
As U.S. health care systems prepare for inpatient surges linked to hospitalizations of critically ill COVID-19 patients, two hospitalists with med-peds training (combined training in internal medicine and pediatrics) have launched an innovative solution to help facilities deal with the challenge.
The Pediatric Overflow Planning Contingency Response Network (POPCoRN network) has quickly linked almost 400 physicians and other health professionals, including hospitalists, attending physicians, residents, medical students, and nurses. The network wants to help provide more information about how pediatric-focused institutions can safely gear up to admit adult patients in children’s hospitals, in order to offset the predicted demand for hospital beds for patients with COVID-19.
According to the POPCoRN network website (www.popcornetwork.org), the majority of providers who have contacted the network say they have already started or are committed to planning for their pediatric facilities to be used for adult overflow. The Children’s Hospital Association has issued a guidance on this kind of community collaboration for children’s hospitals partnering with adult hospitals in their community and with policy makers.
“We are a network of folks from different institutions, many med-peds–trained hospitalists but quickly growing,” said Leah Ratner, MD, a second-year fellow in the Global Pediatrics Program at Boston Children’s Hospital and cofounder of the POPCoRN network. “We came together to think about how to increase capacity – both in the work force and for actual hospital space – by helping to train pediatric hospitalists and pediatrics-trained nurses to care for adult patients.”
A web-based platform filled with a rapidly expanding list of resources, an active Twitter account, and utilization of Zoom networking software for webinars and working group meetings have facilitated the network’s growth. “Social media has helped us,” Dr. Ratner said. But equally important are personal connections.
“It all started just a few weeks ago,” added cofounder Ashley Jenkins, MD, a med-peds hospital medicine and general academics research fellow in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. “I sent out some emails in mid-March, asking what other people were doing about these issues. Leah and I met as a result of these initial emails. We immediately started connecting with other health systems and it just expanded from there. Once we knew that enough other systems were thinking about it and trying to build capacity, we started pulling the people and information together.”
High-yield one-pagers
A third or more of those on the POPCoRN contact list are also participating as volunteers on its varied working groups, including health system operation groups exploring the needs of three distinct hospital models: freestanding children’s hospitals; community hospitals, which may see small numbers of children; and integrated mixed hospitals, which often means a pediatric hospital or pediatric units located within an adult hospital.
An immediate goal is to develop high-yield informational “one-pagers,” culling essential clinical facts on a variety of topics in adult inpatient medicine that may no longer be familiar to working pediatric hospitalists. These one-pagers, designed with the help of network members with graphic design skills, address topics such as syncope or chest pain or managing exacerbation of COPD in adults. They draw upon existing informational sources, encapsulating practical information tips that can be used at the bedside, including test workups, differential diagnoses, treatment approaches, and other pearls for providers. Drafts are reviewed for content by specialists, and then by pediatricians to make sure the information covers what they need.
Also under development are educational materials for nurses trained in pediatrics, a section for outpatient providers redeployed to triage or telehealth, and information for other team members including occupational, physical, and respiratory therapists. Another section offers critical care lectures for the nonintensivist. A metrics and outcomes working group is looking for ways to evaluate how the network is doing and who is being reached without having to ask frontline providers to fill out surveys.
Dr. Ratner and Dr. Jenkins have created an intentional structure for encouraging mentoring. They also call on their own mentors – Ahmet Uluer, DO, director of Weitzman Family Bridges Adult Transition Program at Boston Children’s Hospital, and Brian Herbst Jr., MD, medical director of the Hospital Medicine Adult Care Service at Cincinnati Children’s – for advice.
Beyond the silos
Pediatric hospitalists may have been doing similar things, working on similar projects, but not necessarily reaching out to each other across a system that tends to promote staying within administrative silos, Dr. Uluer said. “Through our personal contacts in POPCoRN, we’ve been able to reach beyond the silos. This network has worked like medical crowd sourcing, and the founders have been inspirational.”
Dr. Herbst added, “How do we expand bandwidth and safely expand services to take young patients and adults from other hospitals? What other populations do we need to expand to take? This network is a workplace of ideas. It’s amazing to see what has been built in a few weeks and how useful it can be.”
Med-peds hospitalists are an important resource for bridging the two specialties. Their experience with transitioning young adults with long-standing chronic conditions of childhood, who have received most of their care at a children’s hospital before reaching adulthood, offers a helpful model. “We’ve also tried to target junior physicians who could step up into leadership roles and to pull in medical students – who are the backbone of this network through their administrative support,” Dr. Jenkins said.
Marie Pfarr, MD, also a med-peds trained hospital medicine fellow at Cincinnati Children’s, was contacted in March by Dr. Jenkins. “She said they had this brainstorm, and they were getting feedback that it would be helpful to provide educational materials for pediatric providers. Because I have an interest in medical education, she asked if I wanted to help. I was at home struggling with what I could contribute during this crazy time, so I said yes.”
Dr. Pfarr leads POPCoRN’s educational working group, which came up with a list of 50 topics in need of one-pagers and people willing to create them, mostly still under development. The aim for the one-pagers is to offer a good starting point for pediatricians, helping them, for example, to ask the right questions during history and physical exams. “We also want to offer additional resources for those who want to do a deeper dive.”
Dr. Pfarr said she has enjoyed working closely with medical students, who really want to help. “That’s been great to see. We are all working toward the same goal, and we help to keep each other in check. I think there’s a future for this kind of mobilization through collaborations to connect pediatric to adult providers. A lot of good things will come out of the network, which is an example of how folks can talk to each other. It’s very dynamic and changing every day.”
One of those medical students is Chinma Onyewuenyi, finishing her fourth year at Baylor College of Medicine. Scheduled to start a med-peds residency at Geisinger Health on July 1, she had completed all of her rotations and was looking for ways to get involved in the pandemic response while respecting the shelter-in-place order. “I had heard about the network, which was recruiting medical students to play administrative roles for the working groups. I said, ‘If you have anything else you need help with, I have time on my hands.’”
Ms. Onyewuenyi says she fell into the role of a lead administrative volunteer, and her responsibilities grew from there, eventually taking charge of all the medical students’ recruiting, screening, and assignments, freeing up the project’s physician leaders from administrative tasks. “I wanted something active to do to contribute, and I appreciate all that I’m learning. With a master’s degree in public health, I have researched how health care is delivered,” she said.
“This experience has really opened my eyes to what’s required to deliver care, and just the level of collaboration that needs to go on with something like this. Even as a medical student, I felt glad to have an opportunity to contribute beyond the administrative tasks. At meetings, they ask for my opinion.”
Equitable access to resources
Another major focus for the network is promoting health equity – giving pediatric providers and health systems equitable access to information that meets their needs, Dr. Ratner said. “We’ve made a particular effort to reach out to hospitals that are the most vulnerable, including rural hospitals, and to those serving the most vulnerable patients,” she noted. These also include the homeless and refugees.
“We’ve been trying to be mindful of avoiding the sometimes-intimidating power structure that has been traditional in medicine,” Dr. Ratner said. The network’s equity working group is trying to provide content with structural competency and cultural humility. “We’re learning a lot about the ways the health care system is broken,” she added. “We all agree that we have a fragmented health care system, but there are ways to make it less fragmented and learn from each other.”
In the tragedy of the COVID epidemic, there are also unique opportunities to learn to work collaboratively and make the health care system stronger for those in greatest need, Dr. Ratner added. “What we hope is that our network becomes an example of that, even as it is moving so quickly.”
Audrey Uong, MD, an attending physician in the division of hospital medicine at Children’s Hospital at Montefiore Medical Center in New York, connected with POPCoRN for an educational presentation reviewing resuscitation in adult patients. She wanted to talk with peers about what’s going on, so as not to feel alone in her practice. She has also found the network’s website useful for identifying educational resources.
“As pediatricians, we have been asked to care for adult patients. One of our units has been admitting mostly patients under age 30, and we are accepting older patients in another unit on the pediatric wing.” This kind of thing is also happening in a lot of other places, Dr. Uong said. Keeping up with these changes in her own practice has been challenging.
She tries to take one day at a time. “Everyone at this institution feels the same – that we’re locked in on meeting the need. Even our child life specialists, when they’re not working with younger patients, have created this amazing support room for staff, with snacks and soothing music. There’s been a lot of attention paid to making us feel supported in this work.”
As U.S. health care systems prepare for inpatient surges linked to hospitalizations of critically ill COVID-19 patients, two hospitalists with med-peds training (combined training in internal medicine and pediatrics) have launched an innovative solution to help facilities deal with the challenge.
The Pediatric Overflow Planning Contingency Response Network (POPCoRN network) has quickly linked almost 400 physicians and other health professionals, including hospitalists, attending physicians, residents, medical students, and nurses. The network wants to help provide more information about how pediatric-focused institutions can safely gear up to admit adult patients in children’s hospitals, in order to offset the predicted demand for hospital beds for patients with COVID-19.
According to the POPCoRN network website (www.popcornetwork.org), the majority of providers who have contacted the network say they have already started or are committed to planning for their pediatric facilities to be used for adult overflow. The Children’s Hospital Association has issued a guidance on this kind of community collaboration for children’s hospitals partnering with adult hospitals in their community and with policy makers.
“We are a network of folks from different institutions, many med-peds–trained hospitalists but quickly growing,” said Leah Ratner, MD, a second-year fellow in the Global Pediatrics Program at Boston Children’s Hospital and cofounder of the POPCoRN network. “We came together to think about how to increase capacity – both in the work force and for actual hospital space – by helping to train pediatric hospitalists and pediatrics-trained nurses to care for adult patients.”
A web-based platform filled with a rapidly expanding list of resources, an active Twitter account, and utilization of Zoom networking software for webinars and working group meetings have facilitated the network’s growth. “Social media has helped us,” Dr. Ratner said. But equally important are personal connections.
“It all started just a few weeks ago,” added cofounder Ashley Jenkins, MD, a med-peds hospital medicine and general academics research fellow in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. “I sent out some emails in mid-March, asking what other people were doing about these issues. Leah and I met as a result of these initial emails. We immediately started connecting with other health systems and it just expanded from there. Once we knew that enough other systems were thinking about it and trying to build capacity, we started pulling the people and information together.”
High-yield one-pagers
A third or more of those on the POPCoRN contact list are also participating as volunteers on its varied working groups, including health system operation groups exploring the needs of three distinct hospital models: freestanding children’s hospitals; community hospitals, which may see small numbers of children; and integrated mixed hospitals, which often means a pediatric hospital or pediatric units located within an adult hospital.
An immediate goal is to develop high-yield informational “one-pagers,” culling essential clinical facts on a variety of topics in adult inpatient medicine that may no longer be familiar to working pediatric hospitalists. These one-pagers, designed with the help of network members with graphic design skills, address topics such as syncope or chest pain or managing exacerbation of COPD in adults. They draw upon existing informational sources, encapsulating practical information tips that can be used at the bedside, including test workups, differential diagnoses, treatment approaches, and other pearls for providers. Drafts are reviewed for content by specialists, and then by pediatricians to make sure the information covers what they need.
Also under development are educational materials for nurses trained in pediatrics, a section for outpatient providers redeployed to triage or telehealth, and information for other team members including occupational, physical, and respiratory therapists. Another section offers critical care lectures for the nonintensivist. A metrics and outcomes working group is looking for ways to evaluate how the network is doing and who is being reached without having to ask frontline providers to fill out surveys.
Dr. Ratner and Dr. Jenkins have created an intentional structure for encouraging mentoring. They also call on their own mentors – Ahmet Uluer, DO, director of Weitzman Family Bridges Adult Transition Program at Boston Children’s Hospital, and Brian Herbst Jr., MD, medical director of the Hospital Medicine Adult Care Service at Cincinnati Children’s – for advice.
Beyond the silos
Pediatric hospitalists may have been doing similar things, working on similar projects, but not necessarily reaching out to each other across a system that tends to promote staying within administrative silos, Dr. Uluer said. “Through our personal contacts in POPCoRN, we’ve been able to reach beyond the silos. This network has worked like medical crowd sourcing, and the founders have been inspirational.”
Dr. Herbst added, “How do we expand bandwidth and safely expand services to take young patients and adults from other hospitals? What other populations do we need to expand to take? This network is a workplace of ideas. It’s amazing to see what has been built in a few weeks and how useful it can be.”
Med-peds hospitalists are an important resource for bridging the two specialties. Their experience with transitioning young adults with long-standing chronic conditions of childhood, who have received most of their care at a children’s hospital before reaching adulthood, offers a helpful model. “We’ve also tried to target junior physicians who could step up into leadership roles and to pull in medical students – who are the backbone of this network through their administrative support,” Dr. Jenkins said.
Marie Pfarr, MD, also a med-peds trained hospital medicine fellow at Cincinnati Children’s, was contacted in March by Dr. Jenkins. “She said they had this brainstorm, and they were getting feedback that it would be helpful to provide educational materials for pediatric providers. Because I have an interest in medical education, she asked if I wanted to help. I was at home struggling with what I could contribute during this crazy time, so I said yes.”
Dr. Pfarr leads POPCoRN’s educational working group, which came up with a list of 50 topics in need of one-pagers and people willing to create them, mostly still under development. The aim for the one-pagers is to offer a good starting point for pediatricians, helping them, for example, to ask the right questions during history and physical exams. “We also want to offer additional resources for those who want to do a deeper dive.”
Dr. Pfarr said she has enjoyed working closely with medical students, who really want to help. “That’s been great to see. We are all working toward the same goal, and we help to keep each other in check. I think there’s a future for this kind of mobilization through collaborations to connect pediatric to adult providers. A lot of good things will come out of the network, which is an example of how folks can talk to each other. It’s very dynamic and changing every day.”
One of those medical students is Chinma Onyewuenyi, finishing her fourth year at Baylor College of Medicine. Scheduled to start a med-peds residency at Geisinger Health on July 1, she had completed all of her rotations and was looking for ways to get involved in the pandemic response while respecting the shelter-in-place order. “I had heard about the network, which was recruiting medical students to play administrative roles for the working groups. I said, ‘If you have anything else you need help with, I have time on my hands.’”
Ms. Onyewuenyi says she fell into the role of a lead administrative volunteer, and her responsibilities grew from there, eventually taking charge of all the medical students’ recruiting, screening, and assignments, freeing up the project’s physician leaders from administrative tasks. “I wanted something active to do to contribute, and I appreciate all that I’m learning. With a master’s degree in public health, I have researched how health care is delivered,” she said.
“This experience has really opened my eyes to what’s required to deliver care, and just the level of collaboration that needs to go on with something like this. Even as a medical student, I felt glad to have an opportunity to contribute beyond the administrative tasks. At meetings, they ask for my opinion.”
Equitable access to resources
Another major focus for the network is promoting health equity – giving pediatric providers and health systems equitable access to information that meets their needs, Dr. Ratner said. “We’ve made a particular effort to reach out to hospitals that are the most vulnerable, including rural hospitals, and to those serving the most vulnerable patients,” she noted. These also include the homeless and refugees.
“We’ve been trying to be mindful of avoiding the sometimes-intimidating power structure that has been traditional in medicine,” Dr. Ratner said. The network’s equity working group is trying to provide content with structural competency and cultural humility. “We’re learning a lot about the ways the health care system is broken,” she added. “We all agree that we have a fragmented health care system, but there are ways to make it less fragmented and learn from each other.”
In the tragedy of the COVID epidemic, there are also unique opportunities to learn to work collaboratively and make the health care system stronger for those in greatest need, Dr. Ratner added. “What we hope is that our network becomes an example of that, even as it is moving so quickly.”
Audrey Uong, MD, an attending physician in the division of hospital medicine at Children’s Hospital at Montefiore Medical Center in New York, connected with POPCoRN for an educational presentation reviewing resuscitation in adult patients. She wanted to talk with peers about what’s going on, so as not to feel alone in her practice. She has also found the network’s website useful for identifying educational resources.
“As pediatricians, we have been asked to care for adult patients. One of our units has been admitting mostly patients under age 30, and we are accepting older patients in another unit on the pediatric wing.” This kind of thing is also happening in a lot of other places, Dr. Uong said. Keeping up with these changes in her own practice has been challenging.
She tries to take one day at a time. “Everyone at this institution feels the same – that we’re locked in on meeting the need. Even our child life specialists, when they’re not working with younger patients, have created this amazing support room for staff, with snacks and soothing music. There’s been a lot of attention paid to making us feel supported in this work.”
Prior head injury is associated with severe Parkinson’s disease phenotype
according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.
Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.
“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
An analysis of data from two cohorts
The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.
In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.
“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”
In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).
“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
The search for the underlying mechanism
Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”
The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.
SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.
according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.
Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.
“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
An analysis of data from two cohorts
The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.
In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.
“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”
In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).
“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
The search for the underlying mechanism
Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”
The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.
SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.
according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.
Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.
“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
An analysis of data from two cohorts
The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.
In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.
“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”
In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).
“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
The search for the underlying mechanism
Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”
The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.
SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.
FROM AAN 2020
Predictors of ICH after thrombectomy identified
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
AAN 2020
CGRP inhibitors receive reassuring real-world safety report
Stephen D. Silberstein, MD, reported online as part of the 2020 American Academy of Neurology Science Highlights.
He presented a retrospective analysis of spontaneous postmarketing reports to the Food and Drug Administration Adverse Events Reporting System (FAERS) for Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), and Emgality (galcanezumab-gnlm).
The top-10 lists of adverse events for all three monoclonal antibodies targeting CGRP were skewed heavily towards injection-site reactions, such as injection-site pain, itching, swelling, and erythema. The rates were relatively low. For example, injection-site pain was reported at a rate of 2.94 cases per 1,000 patients exposed to erenumab, 0.8/1,000 for fremanezumab, and 4.9/1,000 for galcanezumab, according to Dr. Silberstein, professor of neurology and director of the headache center at Sidney Kimmel Medical College, Philadelphia.
Migraine, headache, and drug ineffectiveness were in the top 10 for all three medications, as is typical in FAERS reports, since no drug is effective in everyone. These events were reported at rates of 1-5/1,000 exposed patients. Constipation was reported in association with the use of erenumab at a rate of 4.9 cases/1,000 patients, but did not reach the top-10 lists for the other two CGRP antagonists.
Notably, cardiovascular events were not among the top-10 adverse events reported for any of the novel preventive agents.
“These results will be practice changing, since some physicians have been holding back from prescribing these drugs pending the results of this sort of longer-term safety data,” Dr. Silberstein predicted in an interview.
Asked to comment on the FAERS study, neurologist Holly Yancy, DO, said that she found the findings unsurprising because the adverse effects were essentially as expected based upon the earlier favorable clinical trials experience.
“These medications are living up to the expectations for good tolerability that were in place when they were initially approved by the FDA just under 2 years ago,” said Dr. Yancy, a headache specialist at the Banner–University Medicine Neuroscience Institute in Phoenix.
“Injection-site reactions were anticipated. Clinically, I’ve found that if the medications reduce migraine days and severity, patients find the risk of temporary pain, redness, or itching at the injection site is an easy trade off,” she added.
CGRP is a vasoactive peptide. There has been a theoretic concern that its pharmacologic inhibition for prevention of migraine could lead to an increased risk of adverse cardiovascular events, especially in individuals with coronary disease or a history of stroke. The absence of any such signal during the first 6 months of widespread clinical use of the CGRP inhibitors is highly encouraging, although this is an issue that warrants longer-term study, Dr. Yancy continued.
These drugs, which were expressly designed for migraine prevention, are a considerable advance over what was previously available in her view. They’re equally or more effective and considerably better tolerated than the preventive medications physicians had long been using off label, including antidepressants, antiepileptics, and cardiac drugs.
Dr. Silberstein reported financial relationships with close to two dozen pharmaceutical companies. Dr. Yancy reported serving on speakers’ bureaus for Amgen and Novartis.
SOURCE: Silverstein SD et al. AAN 2020, Abstract S58.008.
Stephen D. Silberstein, MD, reported online as part of the 2020 American Academy of Neurology Science Highlights.
He presented a retrospective analysis of spontaneous postmarketing reports to the Food and Drug Administration Adverse Events Reporting System (FAERS) for Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), and Emgality (galcanezumab-gnlm).
The top-10 lists of adverse events for all three monoclonal antibodies targeting CGRP were skewed heavily towards injection-site reactions, such as injection-site pain, itching, swelling, and erythema. The rates were relatively low. For example, injection-site pain was reported at a rate of 2.94 cases per 1,000 patients exposed to erenumab, 0.8/1,000 for fremanezumab, and 4.9/1,000 for galcanezumab, according to Dr. Silberstein, professor of neurology and director of the headache center at Sidney Kimmel Medical College, Philadelphia.
Migraine, headache, and drug ineffectiveness were in the top 10 for all three medications, as is typical in FAERS reports, since no drug is effective in everyone. These events were reported at rates of 1-5/1,000 exposed patients. Constipation was reported in association with the use of erenumab at a rate of 4.9 cases/1,000 patients, but did not reach the top-10 lists for the other two CGRP antagonists.
Notably, cardiovascular events were not among the top-10 adverse events reported for any of the novel preventive agents.
“These results will be practice changing, since some physicians have been holding back from prescribing these drugs pending the results of this sort of longer-term safety data,” Dr. Silberstein predicted in an interview.
Asked to comment on the FAERS study, neurologist Holly Yancy, DO, said that she found the findings unsurprising because the adverse effects were essentially as expected based upon the earlier favorable clinical trials experience.
“These medications are living up to the expectations for good tolerability that were in place when they were initially approved by the FDA just under 2 years ago,” said Dr. Yancy, a headache specialist at the Banner–University Medicine Neuroscience Institute in Phoenix.
“Injection-site reactions were anticipated. Clinically, I’ve found that if the medications reduce migraine days and severity, patients find the risk of temporary pain, redness, or itching at the injection site is an easy trade off,” she added.
CGRP is a vasoactive peptide. There has been a theoretic concern that its pharmacologic inhibition for prevention of migraine could lead to an increased risk of adverse cardiovascular events, especially in individuals with coronary disease or a history of stroke. The absence of any such signal during the first 6 months of widespread clinical use of the CGRP inhibitors is highly encouraging, although this is an issue that warrants longer-term study, Dr. Yancy continued.
These drugs, which were expressly designed for migraine prevention, are a considerable advance over what was previously available in her view. They’re equally or more effective and considerably better tolerated than the preventive medications physicians had long been using off label, including antidepressants, antiepileptics, and cardiac drugs.
Dr. Silberstein reported financial relationships with close to two dozen pharmaceutical companies. Dr. Yancy reported serving on speakers’ bureaus for Amgen and Novartis.
SOURCE: Silverstein SD et al. AAN 2020, Abstract S58.008.
Stephen D. Silberstein, MD, reported online as part of the 2020 American Academy of Neurology Science Highlights.
He presented a retrospective analysis of spontaneous postmarketing reports to the Food and Drug Administration Adverse Events Reporting System (FAERS) for Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), and Emgality (galcanezumab-gnlm).
The top-10 lists of adverse events for all three monoclonal antibodies targeting CGRP were skewed heavily towards injection-site reactions, such as injection-site pain, itching, swelling, and erythema. The rates were relatively low. For example, injection-site pain was reported at a rate of 2.94 cases per 1,000 patients exposed to erenumab, 0.8/1,000 for fremanezumab, and 4.9/1,000 for galcanezumab, according to Dr. Silberstein, professor of neurology and director of the headache center at Sidney Kimmel Medical College, Philadelphia.
Migraine, headache, and drug ineffectiveness were in the top 10 for all three medications, as is typical in FAERS reports, since no drug is effective in everyone. These events were reported at rates of 1-5/1,000 exposed patients. Constipation was reported in association with the use of erenumab at a rate of 4.9 cases/1,000 patients, but did not reach the top-10 lists for the other two CGRP antagonists.
Notably, cardiovascular events were not among the top-10 adverse events reported for any of the novel preventive agents.
“These results will be practice changing, since some physicians have been holding back from prescribing these drugs pending the results of this sort of longer-term safety data,” Dr. Silberstein predicted in an interview.
Asked to comment on the FAERS study, neurologist Holly Yancy, DO, said that she found the findings unsurprising because the adverse effects were essentially as expected based upon the earlier favorable clinical trials experience.
“These medications are living up to the expectations for good tolerability that were in place when they were initially approved by the FDA just under 2 years ago,” said Dr. Yancy, a headache specialist at the Banner–University Medicine Neuroscience Institute in Phoenix.
“Injection-site reactions were anticipated. Clinically, I’ve found that if the medications reduce migraine days and severity, patients find the risk of temporary pain, redness, or itching at the injection site is an easy trade off,” she added.
CGRP is a vasoactive peptide. There has been a theoretic concern that its pharmacologic inhibition for prevention of migraine could lead to an increased risk of adverse cardiovascular events, especially in individuals with coronary disease or a history of stroke. The absence of any such signal during the first 6 months of widespread clinical use of the CGRP inhibitors is highly encouraging, although this is an issue that warrants longer-term study, Dr. Yancy continued.
These drugs, which were expressly designed for migraine prevention, are a considerable advance over what was previously available in her view. They’re equally or more effective and considerably better tolerated than the preventive medications physicians had long been using off label, including antidepressants, antiepileptics, and cardiac drugs.
Dr. Silberstein reported financial relationships with close to two dozen pharmaceutical companies. Dr. Yancy reported serving on speakers’ bureaus for Amgen and Novartis.
SOURCE: Silverstein SD et al. AAN 2020, Abstract S58.008.
FROM AAN 2020
Anti-NMDAR encephalitis or primary psychiatric disorder?
New insights and ‘red flags’ provide clues to diagnosis
It remains difficult to distinguish anti-NMDA receptor encephalitis from a primary psychiatric disorder, but recent studies have identified clinical features and proposed screening criteria that could make it easier to identify these patients who would benefit from immunotherapy, according to an expert in the neurologic disease.
Most patients with confirmed anti-NMDA receptor encephalitis will experience substantial improvement after treatment with immunotherapy and other modalities, said Josep Dalmau, MD, PhD, professor at the Catalan Institute for Research and Advanced Studies at the University of Barcelona and adjunct professor of neurology at the University of Pennsylvania, Philadelphia.
“In our experience, being aggressive with immune therapy ... the patients do quite well, which means that basically 85%-90% of the patients substantially improved over the next few months,” Dr. Dalmau said at the annual meeting of the American Psychiatric Association, which was held as a virtual live event.
Identified for the first time a little more than a decade ago, anti-NMDA receptor encephalitis is a rare, immune-mediated disease that is usually found in children and young adults and is more common among women. It is frequently associated with ovarian tumors and teratomas, said Dr. Dalmau, and in about 90% of cases, patients will have prominent psychiatric and behavioral symptoms.
Patients develop IgG antibodies against the GluN1 subunit of the NMDA receptor. These autoantibodies represent not only a diagnostic marker of the disease, but are also pathogenic, altering NMDA receptor–related synaptic transmission, Dr. Dalmau said.
In several recent studies, investigators have attempted to cobble together a distinct phenotype on anti-NMDA receptor encephalitis to aid psychiatrists who might encounter patients with the disease, he said.
In one of the most recent studies, researchers combed the medical literature and found that, among 544 individuals with the disease, the most common psychiatric symptoms were agitation, seen in 59%, and psychotic symptoms (particularly visual-auditory hallucinations and disorganized behavior) in 54%; catatonia was seen in 42% of adults and 35% of children.
according to a report from researchers in Berlin, Dr. Dalmau added. By picking up on those clinical signs, which included seizures, catatonia, autonomic instability, or hyperkinesia, the time from symptom onset to diagnosis could be cut in half, the researchers found.
There’s also a handy acronym that could serve as a mnemonic to pick up on “diagnostic clues” of anti-NMDA receptor encephalitis among patients with new-onset psychiatric symptoms, Dr. Dalmau said.
That acronym, published in a review article by Dr. Dalmau and colleagues, is SEARCH For NMDAR-A, covering, in order: sleep dysfunction, excitement, agitation, rapid onset, child and young adult predominance, history of psychiatric disease (absent), fluctuating catatonia, negative and positive symptoms, memory deficit, decreased verbal output, antipsychotic intolerance, rule out neuroleptic malignant syndrome, and of course, antibodies (though the final “A” also stands for additional testing, including magnetic resonance imaging, cerebrospinal fluid studies, and electroencephalogram).
While the disease can be lethal, Dr. Dalmau said most patients respond to immunotherapy, and if applicable, treatment of the underlying tumor can help. The most common first-line treatments include steroids, intravenous immunoglobulin, and plasma exchange, he said, while second-line treatments include the monoclonal anti-CD20 antibody rituximab and cyclophosphamide.
Beyond immunotherapy, patients may benefit from supportive care and psychiatric treatment. Benzodiazepines are well tolerated, but Dr. Dalmau said antipsychotic intolerance is frequent, and electroconvulsive therapy has “mixed results” in these patients.
The recovery process can take months and may be complicated by hypersomnia, hyperphagia, and hypersexuality, he added.
“Some patients improve dramatically in 1 month, but this is uncommon, really,” he said, adding that an early recovery may be a “red flag” that the underlying condition is something other than anti-NMDA receptor encephalitis.
Dr. Dalmau provided disclosures related to Cellex Foundation, Safra Foundation, Caixa Health Project Foundation, and Sage Therapeutics.
SOURCE: Dalmau J. APA 2020, Abstract.
New insights and ‘red flags’ provide clues to diagnosis
New insights and ‘red flags’ provide clues to diagnosis
It remains difficult to distinguish anti-NMDA receptor encephalitis from a primary psychiatric disorder, but recent studies have identified clinical features and proposed screening criteria that could make it easier to identify these patients who would benefit from immunotherapy, according to an expert in the neurologic disease.
Most patients with confirmed anti-NMDA receptor encephalitis will experience substantial improvement after treatment with immunotherapy and other modalities, said Josep Dalmau, MD, PhD, professor at the Catalan Institute for Research and Advanced Studies at the University of Barcelona and adjunct professor of neurology at the University of Pennsylvania, Philadelphia.
“In our experience, being aggressive with immune therapy ... the patients do quite well, which means that basically 85%-90% of the patients substantially improved over the next few months,” Dr. Dalmau said at the annual meeting of the American Psychiatric Association, which was held as a virtual live event.
Identified for the first time a little more than a decade ago, anti-NMDA receptor encephalitis is a rare, immune-mediated disease that is usually found in children and young adults and is more common among women. It is frequently associated with ovarian tumors and teratomas, said Dr. Dalmau, and in about 90% of cases, patients will have prominent psychiatric and behavioral symptoms.
Patients develop IgG antibodies against the GluN1 subunit of the NMDA receptor. These autoantibodies represent not only a diagnostic marker of the disease, but are also pathogenic, altering NMDA receptor–related synaptic transmission, Dr. Dalmau said.
In several recent studies, investigators have attempted to cobble together a distinct phenotype on anti-NMDA receptor encephalitis to aid psychiatrists who might encounter patients with the disease, he said.
In one of the most recent studies, researchers combed the medical literature and found that, among 544 individuals with the disease, the most common psychiatric symptoms were agitation, seen in 59%, and psychotic symptoms (particularly visual-auditory hallucinations and disorganized behavior) in 54%; catatonia was seen in 42% of adults and 35% of children.
according to a report from researchers in Berlin, Dr. Dalmau added. By picking up on those clinical signs, which included seizures, catatonia, autonomic instability, or hyperkinesia, the time from symptom onset to diagnosis could be cut in half, the researchers found.
There’s also a handy acronym that could serve as a mnemonic to pick up on “diagnostic clues” of anti-NMDA receptor encephalitis among patients with new-onset psychiatric symptoms, Dr. Dalmau said.
That acronym, published in a review article by Dr. Dalmau and colleagues, is SEARCH For NMDAR-A, covering, in order: sleep dysfunction, excitement, agitation, rapid onset, child and young adult predominance, history of psychiatric disease (absent), fluctuating catatonia, negative and positive symptoms, memory deficit, decreased verbal output, antipsychotic intolerance, rule out neuroleptic malignant syndrome, and of course, antibodies (though the final “A” also stands for additional testing, including magnetic resonance imaging, cerebrospinal fluid studies, and electroencephalogram).
While the disease can be lethal, Dr. Dalmau said most patients respond to immunotherapy, and if applicable, treatment of the underlying tumor can help. The most common first-line treatments include steroids, intravenous immunoglobulin, and plasma exchange, he said, while second-line treatments include the monoclonal anti-CD20 antibody rituximab and cyclophosphamide.
Beyond immunotherapy, patients may benefit from supportive care and psychiatric treatment. Benzodiazepines are well tolerated, but Dr. Dalmau said antipsychotic intolerance is frequent, and electroconvulsive therapy has “mixed results” in these patients.
The recovery process can take months and may be complicated by hypersomnia, hyperphagia, and hypersexuality, he added.
“Some patients improve dramatically in 1 month, but this is uncommon, really,” he said, adding that an early recovery may be a “red flag” that the underlying condition is something other than anti-NMDA receptor encephalitis.
Dr. Dalmau provided disclosures related to Cellex Foundation, Safra Foundation, Caixa Health Project Foundation, and Sage Therapeutics.
SOURCE: Dalmau J. APA 2020, Abstract.
It remains difficult to distinguish anti-NMDA receptor encephalitis from a primary psychiatric disorder, but recent studies have identified clinical features and proposed screening criteria that could make it easier to identify these patients who would benefit from immunotherapy, according to an expert in the neurologic disease.
Most patients with confirmed anti-NMDA receptor encephalitis will experience substantial improvement after treatment with immunotherapy and other modalities, said Josep Dalmau, MD, PhD, professor at the Catalan Institute for Research and Advanced Studies at the University of Barcelona and adjunct professor of neurology at the University of Pennsylvania, Philadelphia.
“In our experience, being aggressive with immune therapy ... the patients do quite well, which means that basically 85%-90% of the patients substantially improved over the next few months,” Dr. Dalmau said at the annual meeting of the American Psychiatric Association, which was held as a virtual live event.
Identified for the first time a little more than a decade ago, anti-NMDA receptor encephalitis is a rare, immune-mediated disease that is usually found in children and young adults and is more common among women. It is frequently associated with ovarian tumors and teratomas, said Dr. Dalmau, and in about 90% of cases, patients will have prominent psychiatric and behavioral symptoms.
Patients develop IgG antibodies against the GluN1 subunit of the NMDA receptor. These autoantibodies represent not only a diagnostic marker of the disease, but are also pathogenic, altering NMDA receptor–related synaptic transmission, Dr. Dalmau said.
In several recent studies, investigators have attempted to cobble together a distinct phenotype on anti-NMDA receptor encephalitis to aid psychiatrists who might encounter patients with the disease, he said.
In one of the most recent studies, researchers combed the medical literature and found that, among 544 individuals with the disease, the most common psychiatric symptoms were agitation, seen in 59%, and psychotic symptoms (particularly visual-auditory hallucinations and disorganized behavior) in 54%; catatonia was seen in 42% of adults and 35% of children.
according to a report from researchers in Berlin, Dr. Dalmau added. By picking up on those clinical signs, which included seizures, catatonia, autonomic instability, or hyperkinesia, the time from symptom onset to diagnosis could be cut in half, the researchers found.
There’s also a handy acronym that could serve as a mnemonic to pick up on “diagnostic clues” of anti-NMDA receptor encephalitis among patients with new-onset psychiatric symptoms, Dr. Dalmau said.
That acronym, published in a review article by Dr. Dalmau and colleagues, is SEARCH For NMDAR-A, covering, in order: sleep dysfunction, excitement, agitation, rapid onset, child and young adult predominance, history of psychiatric disease (absent), fluctuating catatonia, negative and positive symptoms, memory deficit, decreased verbal output, antipsychotic intolerance, rule out neuroleptic malignant syndrome, and of course, antibodies (though the final “A” also stands for additional testing, including magnetic resonance imaging, cerebrospinal fluid studies, and electroencephalogram).
While the disease can be lethal, Dr. Dalmau said most patients respond to immunotherapy, and if applicable, treatment of the underlying tumor can help. The most common first-line treatments include steroids, intravenous immunoglobulin, and plasma exchange, he said, while second-line treatments include the monoclonal anti-CD20 antibody rituximab and cyclophosphamide.
Beyond immunotherapy, patients may benefit from supportive care and psychiatric treatment. Benzodiazepines are well tolerated, but Dr. Dalmau said antipsychotic intolerance is frequent, and electroconvulsive therapy has “mixed results” in these patients.
The recovery process can take months and may be complicated by hypersomnia, hyperphagia, and hypersexuality, he added.
“Some patients improve dramatically in 1 month, but this is uncommon, really,” he said, adding that an early recovery may be a “red flag” that the underlying condition is something other than anti-NMDA receptor encephalitis.
Dr. Dalmau provided disclosures related to Cellex Foundation, Safra Foundation, Caixa Health Project Foundation, and Sage Therapeutics.
SOURCE: Dalmau J. APA 2020, Abstract.
FROM APA 2020
Report details first case of PML with ocrelizumab alone
The case report was presented online as part of the 2020 American Academy of Neurology Science Highlights.
PML, an opportunistic infection of the brain caused by reactivation of the John Cunningham (JC) virus, has occurred with rituximab, another anti-CD20 therapy, in rare cases. Eight other cases of PML diagnosed after ocrelizumab initiation are considered carry-over cases related to prior treatment with natalizumab or fingolimod, according to Genentech, the manufacturer of ocrelizumab. No other PML cases have been associated with ocrelizumab alone.
The case without prior MS treatment was in a 78-year-old man. He presented with 2 weeks of progressive visual disturbance and confusion, said Marc L. Gordon, MD, chief of neurology at the Zucker Hillside Hospital in Glen Oaks, N.Y., and professor of neurology and psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, N.Y.
The patient had a right homonymous hemianopia. “MRI revealed an enlarging non-enhancing left parietal lesion without mass effect,” reported Dr. Gordon and colleagues. “CSF PCR revealed 1,000 copies/mL of JCV, confirming the diagnosis of PML. Blood work upon diagnosis revealed grade-2 lymphopenia ... and negative HIV serology.”
“The patient’s symptoms progressed over weeks to involve bilateral visual loss, right facial droop, and dysphasia,” they said. “Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated.” The patient did not respond to therapy and became bedbound, Dr. Gordon said in an interview. The patient received palliative care and died. An autopsy is pending.
“PML occurrence may have been multifactorial, due to a combination of the immunomodulatory function of ocrelizumab, possible immune senescence, and preceding mild lymphopenia,” Dr. Gordon and coauthors said. “This case emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections, such as the elderly.”
The patient, who was Dr. Gordon’s patient for 20 years, had monitored updates in drug development and had looked forward to starting ocrelizumab, the first therapy approved for primary progressive MS, when it became available after its approval in 2017. The patient was concerned about progressively worsening gait impairment and related falls caused by MS.
Antibodies indicated that the patient had prior exposure to JCV, but Dr. Gordon considered the risk of PML to be relatively small. Prior to treatment, the patient’s absolute lymphocyte count was normal or indicated mild lymphocytopenia, which Dr. Gordon did not consider clinically significant. The patient received ocrelizumab for 2 years without incident.
In an information sheet for health care professionals about ocrelizumab and PML prepared in February 2020, Genentech says the patient’s age and low absolute lymphocyte count are confounding factors, which distort “the assessment of association between exposure to a drug and an adverse event.
“As of January 31, 2020, no unconfounded PML cases associated with ocrelizumab therapy have been reported,” according to the document. “Out of more than 150,000 patients treated globally (clinical trials and post-marketing experience), there have been nine confirmed, confounded cases of PML in patients treated with ocrelizumab, of which eight were carry-over cases from a prior DMT.”
The prescribing information for the drug notes that no cases of PML were identified in ocrelizumab clinical trials, but that PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies. In addition, PML “has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants).
“At the first sign or symptom suggestive of PML, withhold ocrelizumab and perform an appropriate diagnostic evaluation,” the prescribing information says. “MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.”
“It is important for people to recognize that this is at least a possibility,” Dr. Gordon said. Any change in clinical symptomatology may warrant imaging, and CSF testing may be warranted if an MRI raises concerns about PML, he said.
Dr. Gordon has received research support from MSD (Merck), Eisai, AbbVie, and Janssen.
SOURCE: Sul J et al. AAN 2020. Abstract S29.001.
The case report was presented online as part of the 2020 American Academy of Neurology Science Highlights.
PML, an opportunistic infection of the brain caused by reactivation of the John Cunningham (JC) virus, has occurred with rituximab, another anti-CD20 therapy, in rare cases. Eight other cases of PML diagnosed after ocrelizumab initiation are considered carry-over cases related to prior treatment with natalizumab or fingolimod, according to Genentech, the manufacturer of ocrelizumab. No other PML cases have been associated with ocrelizumab alone.
The case without prior MS treatment was in a 78-year-old man. He presented with 2 weeks of progressive visual disturbance and confusion, said Marc L. Gordon, MD, chief of neurology at the Zucker Hillside Hospital in Glen Oaks, N.Y., and professor of neurology and psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, N.Y.
The patient had a right homonymous hemianopia. “MRI revealed an enlarging non-enhancing left parietal lesion without mass effect,” reported Dr. Gordon and colleagues. “CSF PCR revealed 1,000 copies/mL of JCV, confirming the diagnosis of PML. Blood work upon diagnosis revealed grade-2 lymphopenia ... and negative HIV serology.”
“The patient’s symptoms progressed over weeks to involve bilateral visual loss, right facial droop, and dysphasia,” they said. “Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated.” The patient did not respond to therapy and became bedbound, Dr. Gordon said in an interview. The patient received palliative care and died. An autopsy is pending.
“PML occurrence may have been multifactorial, due to a combination of the immunomodulatory function of ocrelizumab, possible immune senescence, and preceding mild lymphopenia,” Dr. Gordon and coauthors said. “This case emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections, such as the elderly.”
The patient, who was Dr. Gordon’s patient for 20 years, had monitored updates in drug development and had looked forward to starting ocrelizumab, the first therapy approved for primary progressive MS, when it became available after its approval in 2017. The patient was concerned about progressively worsening gait impairment and related falls caused by MS.
Antibodies indicated that the patient had prior exposure to JCV, but Dr. Gordon considered the risk of PML to be relatively small. Prior to treatment, the patient’s absolute lymphocyte count was normal or indicated mild lymphocytopenia, which Dr. Gordon did not consider clinically significant. The patient received ocrelizumab for 2 years without incident.
In an information sheet for health care professionals about ocrelizumab and PML prepared in February 2020, Genentech says the patient’s age and low absolute lymphocyte count are confounding factors, which distort “the assessment of association between exposure to a drug and an adverse event.
“As of January 31, 2020, no unconfounded PML cases associated with ocrelizumab therapy have been reported,” according to the document. “Out of more than 150,000 patients treated globally (clinical trials and post-marketing experience), there have been nine confirmed, confounded cases of PML in patients treated with ocrelizumab, of which eight were carry-over cases from a prior DMT.”
The prescribing information for the drug notes that no cases of PML were identified in ocrelizumab clinical trials, but that PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies. In addition, PML “has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants).
“At the first sign or symptom suggestive of PML, withhold ocrelizumab and perform an appropriate diagnostic evaluation,” the prescribing information says. “MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.”
“It is important for people to recognize that this is at least a possibility,” Dr. Gordon said. Any change in clinical symptomatology may warrant imaging, and CSF testing may be warranted if an MRI raises concerns about PML, he said.
Dr. Gordon has received research support from MSD (Merck), Eisai, AbbVie, and Janssen.
SOURCE: Sul J et al. AAN 2020. Abstract S29.001.
The case report was presented online as part of the 2020 American Academy of Neurology Science Highlights.
PML, an opportunistic infection of the brain caused by reactivation of the John Cunningham (JC) virus, has occurred with rituximab, another anti-CD20 therapy, in rare cases. Eight other cases of PML diagnosed after ocrelizumab initiation are considered carry-over cases related to prior treatment with natalizumab or fingolimod, according to Genentech, the manufacturer of ocrelizumab. No other PML cases have been associated with ocrelizumab alone.
The case without prior MS treatment was in a 78-year-old man. He presented with 2 weeks of progressive visual disturbance and confusion, said Marc L. Gordon, MD, chief of neurology at the Zucker Hillside Hospital in Glen Oaks, N.Y., and professor of neurology and psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, N.Y.
The patient had a right homonymous hemianopia. “MRI revealed an enlarging non-enhancing left parietal lesion without mass effect,” reported Dr. Gordon and colleagues. “CSF PCR revealed 1,000 copies/mL of JCV, confirming the diagnosis of PML. Blood work upon diagnosis revealed grade-2 lymphopenia ... and negative HIV serology.”
“The patient’s symptoms progressed over weeks to involve bilateral visual loss, right facial droop, and dysphasia,” they said. “Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated.” The patient did not respond to therapy and became bedbound, Dr. Gordon said in an interview. The patient received palliative care and died. An autopsy is pending.
“PML occurrence may have been multifactorial, due to a combination of the immunomodulatory function of ocrelizumab, possible immune senescence, and preceding mild lymphopenia,” Dr. Gordon and coauthors said. “This case emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections, such as the elderly.”
The patient, who was Dr. Gordon’s patient for 20 years, had monitored updates in drug development and had looked forward to starting ocrelizumab, the first therapy approved for primary progressive MS, when it became available after its approval in 2017. The patient was concerned about progressively worsening gait impairment and related falls caused by MS.
Antibodies indicated that the patient had prior exposure to JCV, but Dr. Gordon considered the risk of PML to be relatively small. Prior to treatment, the patient’s absolute lymphocyte count was normal or indicated mild lymphocytopenia, which Dr. Gordon did not consider clinically significant. The patient received ocrelizumab for 2 years without incident.
In an information sheet for health care professionals about ocrelizumab and PML prepared in February 2020, Genentech says the patient’s age and low absolute lymphocyte count are confounding factors, which distort “the assessment of association between exposure to a drug and an adverse event.
“As of January 31, 2020, no unconfounded PML cases associated with ocrelizumab therapy have been reported,” according to the document. “Out of more than 150,000 patients treated globally (clinical trials and post-marketing experience), there have been nine confirmed, confounded cases of PML in patients treated with ocrelizumab, of which eight were carry-over cases from a prior DMT.”
The prescribing information for the drug notes that no cases of PML were identified in ocrelizumab clinical trials, but that PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies. In addition, PML “has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants).
“At the first sign or symptom suggestive of PML, withhold ocrelizumab and perform an appropriate diagnostic evaluation,” the prescribing information says. “MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.”
“It is important for people to recognize that this is at least a possibility,” Dr. Gordon said. Any change in clinical symptomatology may warrant imaging, and CSF testing may be warranted if an MRI raises concerns about PML, he said.
Dr. Gordon has received research support from MSD (Merck), Eisai, AbbVie, and Janssen.
SOURCE: Sul J et al. AAN 2020. Abstract S29.001.
FROM AAN 2020
COVID-19: An opportunity, challenge for addiction treatment, NIDA boss says
The COVID-19 pandemic is posing significant challenges while also providing unique opportunities for patients with substance use disorders (SUD), a leading expert says.
Nora Volkow, MD, director of the National Institute on Drug Abuse, said that the pandemic has accelerated the use of telemedicine, making it easier for patients with SUD to access treatment. It has also led to the proliferation of more mental health hotlines, which is critical since the vast majority of these patients have comorbid mental illness.
In addition, COVID-19 has resulted in increased availability of “alternative” peer support mechanisms via cellphones or computers to aid individuals’ sobriety.
Dr. Volkow spoke at the virtual American Psychiatric Association Spring Highlights Meeting 2020, which is replacing the organization’s canceled annual meeting.
While methadone clinics have had to close during the pandemic, making it challenging for those on medically assisted treatment to receive methadone or buprenorphine, some of the rules and regulations have been relaxed in order to make these medications accessible without the need for in-person attendance at a clinic. In addition, the Substance Abuse and Mental Health Services Administration has relaxed some of its own regulations regarding telehealth and opioid treatment programs.
Social isolation, stigma intensified
A pandemic increases anxiety in the general population, but for patients with SUD who may be also be struggling with homelessness and comorbid mental illness, the situation can further exacerbate social stigma and isolation – leading to relapse, more overdoses, and overdose deaths, Dr. Volkow said. Social interaction is “extraordinarily important” for patients and “one of the most powerful tools we have” to build resilience.
Right now, said Dr. Volkow, “we are in the dark as to how COVID infections have affected the number of overdose deaths.”
However, she noted that
“So even through this devastation, we can actually extract something that may help others in future,” she said.
Dr. Volkow noted that during the pandemic it is critical to reinforce the importance of engaging in – and remaining in – treatment to SUD patients. It’s also crucial to make patients aware of social support systems and behavioral interventions to help them cope with stress and to mitigate relapse risk.
COVID-19 and relapse
Elie G. Aoun, MD, assistant professor of psychiatry at New York University and vice chair of the APA’s Council on Addiction Psychiatry, said in an interview that Dr. Volkow’s presentation provided “exactly the kind of accessible information” clinicians need.
Dr. Aoun said he sees the impact of the COVID-19 crisis in his practice every day. Patients with SUD “are getting the short end of the stick.”
Social distancing measures prompted by the pandemic can be “very triggering” for SUD patients, he said. One of his patients told him the current isolation, loneliness, movement restrictions, and boredom remind her of the way she felt when she used drugs.
Dr. Aoun said four of his patients have relapsed since the pandemic began. Two of them had just started treatment after years of using drugs, so this was a “major setback” for them.
He and his colleagues were “not really prepared” to provide care via video link, which he believes is not as effective as in-person sessions.
In addition to disrupting patient care, said Dr. Aoun, the pandemic is forcing the medical community to face social determinants of health, such as poverty and homelessness, as they relate to addiction disorders and whether or not someone receives care.
This article originally appeared on Medscape.com.
The COVID-19 pandemic is posing significant challenges while also providing unique opportunities for patients with substance use disorders (SUD), a leading expert says.
Nora Volkow, MD, director of the National Institute on Drug Abuse, said that the pandemic has accelerated the use of telemedicine, making it easier for patients with SUD to access treatment. It has also led to the proliferation of more mental health hotlines, which is critical since the vast majority of these patients have comorbid mental illness.
In addition, COVID-19 has resulted in increased availability of “alternative” peer support mechanisms via cellphones or computers to aid individuals’ sobriety.
Dr. Volkow spoke at the virtual American Psychiatric Association Spring Highlights Meeting 2020, which is replacing the organization’s canceled annual meeting.
While methadone clinics have had to close during the pandemic, making it challenging for those on medically assisted treatment to receive methadone or buprenorphine, some of the rules and regulations have been relaxed in order to make these medications accessible without the need for in-person attendance at a clinic. In addition, the Substance Abuse and Mental Health Services Administration has relaxed some of its own regulations regarding telehealth and opioid treatment programs.
Social isolation, stigma intensified
A pandemic increases anxiety in the general population, but for patients with SUD who may be also be struggling with homelessness and comorbid mental illness, the situation can further exacerbate social stigma and isolation – leading to relapse, more overdoses, and overdose deaths, Dr. Volkow said. Social interaction is “extraordinarily important” for patients and “one of the most powerful tools we have” to build resilience.
Right now, said Dr. Volkow, “we are in the dark as to how COVID infections have affected the number of overdose deaths.”
However, she noted that
“So even through this devastation, we can actually extract something that may help others in future,” she said.
Dr. Volkow noted that during the pandemic it is critical to reinforce the importance of engaging in – and remaining in – treatment to SUD patients. It’s also crucial to make patients aware of social support systems and behavioral interventions to help them cope with stress and to mitigate relapse risk.
COVID-19 and relapse
Elie G. Aoun, MD, assistant professor of psychiatry at New York University and vice chair of the APA’s Council on Addiction Psychiatry, said in an interview that Dr. Volkow’s presentation provided “exactly the kind of accessible information” clinicians need.
Dr. Aoun said he sees the impact of the COVID-19 crisis in his practice every day. Patients with SUD “are getting the short end of the stick.”
Social distancing measures prompted by the pandemic can be “very triggering” for SUD patients, he said. One of his patients told him the current isolation, loneliness, movement restrictions, and boredom remind her of the way she felt when she used drugs.
Dr. Aoun said four of his patients have relapsed since the pandemic began. Two of them had just started treatment after years of using drugs, so this was a “major setback” for them.
He and his colleagues were “not really prepared” to provide care via video link, which he believes is not as effective as in-person sessions.
In addition to disrupting patient care, said Dr. Aoun, the pandemic is forcing the medical community to face social determinants of health, such as poverty and homelessness, as they relate to addiction disorders and whether or not someone receives care.
This article originally appeared on Medscape.com.
The COVID-19 pandemic is posing significant challenges while also providing unique opportunities for patients with substance use disorders (SUD), a leading expert says.
Nora Volkow, MD, director of the National Institute on Drug Abuse, said that the pandemic has accelerated the use of telemedicine, making it easier for patients with SUD to access treatment. It has also led to the proliferation of more mental health hotlines, which is critical since the vast majority of these patients have comorbid mental illness.
In addition, COVID-19 has resulted in increased availability of “alternative” peer support mechanisms via cellphones or computers to aid individuals’ sobriety.
Dr. Volkow spoke at the virtual American Psychiatric Association Spring Highlights Meeting 2020, which is replacing the organization’s canceled annual meeting.
While methadone clinics have had to close during the pandemic, making it challenging for those on medically assisted treatment to receive methadone or buprenorphine, some of the rules and regulations have been relaxed in order to make these medications accessible without the need for in-person attendance at a clinic. In addition, the Substance Abuse and Mental Health Services Administration has relaxed some of its own regulations regarding telehealth and opioid treatment programs.
Social isolation, stigma intensified
A pandemic increases anxiety in the general population, but for patients with SUD who may be also be struggling with homelessness and comorbid mental illness, the situation can further exacerbate social stigma and isolation – leading to relapse, more overdoses, and overdose deaths, Dr. Volkow said. Social interaction is “extraordinarily important” for patients and “one of the most powerful tools we have” to build resilience.
Right now, said Dr. Volkow, “we are in the dark as to how COVID infections have affected the number of overdose deaths.”
However, she noted that
“So even through this devastation, we can actually extract something that may help others in future,” she said.
Dr. Volkow noted that during the pandemic it is critical to reinforce the importance of engaging in – and remaining in – treatment to SUD patients. It’s also crucial to make patients aware of social support systems and behavioral interventions to help them cope with stress and to mitigate relapse risk.
COVID-19 and relapse
Elie G. Aoun, MD, assistant professor of psychiatry at New York University and vice chair of the APA’s Council on Addiction Psychiatry, said in an interview that Dr. Volkow’s presentation provided “exactly the kind of accessible information” clinicians need.
Dr. Aoun said he sees the impact of the COVID-19 crisis in his practice every day. Patients with SUD “are getting the short end of the stick.”
Social distancing measures prompted by the pandemic can be “very triggering” for SUD patients, he said. One of his patients told him the current isolation, loneliness, movement restrictions, and boredom remind her of the way she felt when she used drugs.
Dr. Aoun said four of his patients have relapsed since the pandemic began. Two of them had just started treatment after years of using drugs, so this was a “major setback” for them.
He and his colleagues were “not really prepared” to provide care via video link, which he believes is not as effective as in-person sessions.
In addition to disrupting patient care, said Dr. Aoun, the pandemic is forcing the medical community to face social determinants of health, such as poverty and homelessness, as they relate to addiction disorders and whether or not someone receives care.
This article originally appeared on Medscape.com.