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Children’s share of COVID-19 burden has never been higher
For the first time since the pandemic began, children’s share of weekly COVID-19 cases topped 20% in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
That represented 20.6% of all new cases for the week, eclipsing the previous high of 19.1% recorded just 3 weeks ago, based on data collected by the AAP and CHA from 49 states, the District of Columbia, New York City, Puerto Rico, and Guam.
Cumulative cases of COVID-19 in children exceed 3.6 million in those jurisdictions, which is 13.6% of the total reported among all ages, and the overall rate of coronavirus infection is 4,824 cases per 100,000 children in the population, the AAP and CHA said in their weekly COVID-19 report.
Among the 53 reporting jurisdictions, North Dakota has the highest cumulative rate, 9,167 per 100,000 children, followed by Tennessee (8,580), South Carolina (7,948), South Dakota (7,938), and Connecticut (7,707). Children’s share of cumulative cases is highest in Vermont, at 21.9%, with Alaska next at 20.0% and Wyoming at 19.2%, the AAP and CHA said.
Since the beginning of April, the largest local increases in cases reported came in Michigan (21.6%), Vermont (15.9%), and Maine (15.6%). Nationally, the increase over those same 2 weeks is just under 5%, the two organizations noted.
There were 5 deaths among children during the week of April 9-15, bringing the total to 297, but the recent increases in cases have not affected the long-term trends for serious illness. The death rate for children with COVID-19 has been 0.01% since early November – 43 states, New York City, Puerto Rico, and Guam are reporting such data – and the hospitalization rate has been 0.8% since mid-January in 24 states and New York City, the AAP/CHA data show.
For the first time since the pandemic began, children’s share of weekly COVID-19 cases topped 20% in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
That represented 20.6% of all new cases for the week, eclipsing the previous high of 19.1% recorded just 3 weeks ago, based on data collected by the AAP and CHA from 49 states, the District of Columbia, New York City, Puerto Rico, and Guam.
Cumulative cases of COVID-19 in children exceed 3.6 million in those jurisdictions, which is 13.6% of the total reported among all ages, and the overall rate of coronavirus infection is 4,824 cases per 100,000 children in the population, the AAP and CHA said in their weekly COVID-19 report.
Among the 53 reporting jurisdictions, North Dakota has the highest cumulative rate, 9,167 per 100,000 children, followed by Tennessee (8,580), South Carolina (7,948), South Dakota (7,938), and Connecticut (7,707). Children’s share of cumulative cases is highest in Vermont, at 21.9%, with Alaska next at 20.0% and Wyoming at 19.2%, the AAP and CHA said.
Since the beginning of April, the largest local increases in cases reported came in Michigan (21.6%), Vermont (15.9%), and Maine (15.6%). Nationally, the increase over those same 2 weeks is just under 5%, the two organizations noted.
There were 5 deaths among children during the week of April 9-15, bringing the total to 297, but the recent increases in cases have not affected the long-term trends for serious illness. The death rate for children with COVID-19 has been 0.01% since early November – 43 states, New York City, Puerto Rico, and Guam are reporting such data – and the hospitalization rate has been 0.8% since mid-January in 24 states and New York City, the AAP/CHA data show.
For the first time since the pandemic began, children’s share of weekly COVID-19 cases topped 20% in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
That represented 20.6% of all new cases for the week, eclipsing the previous high of 19.1% recorded just 3 weeks ago, based on data collected by the AAP and CHA from 49 states, the District of Columbia, New York City, Puerto Rico, and Guam.
Cumulative cases of COVID-19 in children exceed 3.6 million in those jurisdictions, which is 13.6% of the total reported among all ages, and the overall rate of coronavirus infection is 4,824 cases per 100,000 children in the population, the AAP and CHA said in their weekly COVID-19 report.
Among the 53 reporting jurisdictions, North Dakota has the highest cumulative rate, 9,167 per 100,000 children, followed by Tennessee (8,580), South Carolina (7,948), South Dakota (7,938), and Connecticut (7,707). Children’s share of cumulative cases is highest in Vermont, at 21.9%, with Alaska next at 20.0% and Wyoming at 19.2%, the AAP and CHA said.
Since the beginning of April, the largest local increases in cases reported came in Michigan (21.6%), Vermont (15.9%), and Maine (15.6%). Nationally, the increase over those same 2 weeks is just under 5%, the two organizations noted.
There were 5 deaths among children during the week of April 9-15, bringing the total to 297, but the recent increases in cases have not affected the long-term trends for serious illness. The death rate for children with COVID-19 has been 0.01% since early November – 43 states, New York City, Puerto Rico, and Guam are reporting such data – and the hospitalization rate has been 0.8% since mid-January in 24 states and New York City, the AAP/CHA data show.
VEXAS syndrome: Implications for dermatologists
When I was a medical student, I always found it gratifying when there was a unifying mechanism that explained the symptoms of a disease. Part of the reason I chose dermatology as a specialty was how frequently we are able to “see” these mechanisms in the skin, both clinically and histologically. What’s even more interesting is that this condition is caused by a postzygotic somatic mutation, an apparently underrecognized cause of disease that we are just now beginning to understand. An example of a postzygotic somatic mutation causing a disease that we all learned about in medical school is paroxysmal nocturnal hemoglobinuria.
Using a “bottom-up” approach, researchers at the National Institutes of Health and in the United Kingdom identified 25 patients with somatic UBA1 mutations and noticed that they had strikingly similar autoinflammatory syndromes. UBA1 encodes ubiquitin E1, which is part of the pathway the breaks down proteins as part of the normal cellular machine. It is localized to the X chromosome, so all 25 affected patients were males, and most were aged between 40 and 70 years. These patients had an autoinflammatory syndrome characterized by fever, chondritis (similar to relapsing polychondritis), vasculitis, and neutrophilic dermatoses. Many patients also had features of myelodysplastic syndrome and plasma cell dyscrasia. The inflammatory pattern in this condition seems to show elevations in tumor necrosis factor, interleukin-6, and interferon-gamma.
So why is this syndrome relevant to dermatology? We are often asked to evaluate patients for neutrophilic dermatosis and vasculitis, and many affected patients had clinical and histologic findings compatible with polyarteritis nodosa and Sweet syndrome. When confronted with a neutrophilic dermatosis, we’ve all been taught to evaluate for myelodysplastic syndrome, which many of these patients appeared to have, at least on the surface. When bone marrow biopsies were done, the myeloid cell precursors that give rise to neutrophils were noted to have prominent cytoplasmic vacuoles, hence the “V” in VEXAS.
In reading the article describing 25 patients with this syndrome, which was published in the New England Journal of Medicine, I was struck by how refractory they were to treatment. Most patients had been treated with systemic steroids, multiple biologics, and several nonbiologic medications that are mainstays of treatment for neutrophilic dermatosis like dapsone and colchicine. I was fortunate enough to speak to Amanda Ombrello, MD, of the National Human Genome Research Institute, one of the lead authors of the paper, who drew my attention to the supplementary appendix, which showed the marked injection-site reactions some patients had to anakinra – yet another reason why a patient might end up in a dermatology clinic. In my mind, all of these features could be a clue to a diagnosis of VEXAS syndrome.
Many patients seemed to fare poorly, with 40% of patients dying before the completion of the study. When it comes to extremely rare diseases, it seems that the more physicians who are aware of the existence of a particular syndrome, the more likely it is a patient will come under our care and be correctly diagnosed.
Dr. Saardi is a dermatologist and internist, and is director of the inpatient dermatology service at the George Washington University Hospital, Washington. He has no disclosures.
When I was a medical student, I always found it gratifying when there was a unifying mechanism that explained the symptoms of a disease. Part of the reason I chose dermatology as a specialty was how frequently we are able to “see” these mechanisms in the skin, both clinically and histologically. What’s even more interesting is that this condition is caused by a postzygotic somatic mutation, an apparently underrecognized cause of disease that we are just now beginning to understand. An example of a postzygotic somatic mutation causing a disease that we all learned about in medical school is paroxysmal nocturnal hemoglobinuria.
Using a “bottom-up” approach, researchers at the National Institutes of Health and in the United Kingdom identified 25 patients with somatic UBA1 mutations and noticed that they had strikingly similar autoinflammatory syndromes. UBA1 encodes ubiquitin E1, which is part of the pathway the breaks down proteins as part of the normal cellular machine. It is localized to the X chromosome, so all 25 affected patients were males, and most were aged between 40 and 70 years. These patients had an autoinflammatory syndrome characterized by fever, chondritis (similar to relapsing polychondritis), vasculitis, and neutrophilic dermatoses. Many patients also had features of myelodysplastic syndrome and plasma cell dyscrasia. The inflammatory pattern in this condition seems to show elevations in tumor necrosis factor, interleukin-6, and interferon-gamma.
So why is this syndrome relevant to dermatology? We are often asked to evaluate patients for neutrophilic dermatosis and vasculitis, and many affected patients had clinical and histologic findings compatible with polyarteritis nodosa and Sweet syndrome. When confronted with a neutrophilic dermatosis, we’ve all been taught to evaluate for myelodysplastic syndrome, which many of these patients appeared to have, at least on the surface. When bone marrow biopsies were done, the myeloid cell precursors that give rise to neutrophils were noted to have prominent cytoplasmic vacuoles, hence the “V” in VEXAS.
In reading the article describing 25 patients with this syndrome, which was published in the New England Journal of Medicine, I was struck by how refractory they were to treatment. Most patients had been treated with systemic steroids, multiple biologics, and several nonbiologic medications that are mainstays of treatment for neutrophilic dermatosis like dapsone and colchicine. I was fortunate enough to speak to Amanda Ombrello, MD, of the National Human Genome Research Institute, one of the lead authors of the paper, who drew my attention to the supplementary appendix, which showed the marked injection-site reactions some patients had to anakinra – yet another reason why a patient might end up in a dermatology clinic. In my mind, all of these features could be a clue to a diagnosis of VEXAS syndrome.
Many patients seemed to fare poorly, with 40% of patients dying before the completion of the study. When it comes to extremely rare diseases, it seems that the more physicians who are aware of the existence of a particular syndrome, the more likely it is a patient will come under our care and be correctly diagnosed.
Dr. Saardi is a dermatologist and internist, and is director of the inpatient dermatology service at the George Washington University Hospital, Washington. He has no disclosures.
When I was a medical student, I always found it gratifying when there was a unifying mechanism that explained the symptoms of a disease. Part of the reason I chose dermatology as a specialty was how frequently we are able to “see” these mechanisms in the skin, both clinically and histologically. What’s even more interesting is that this condition is caused by a postzygotic somatic mutation, an apparently underrecognized cause of disease that we are just now beginning to understand. An example of a postzygotic somatic mutation causing a disease that we all learned about in medical school is paroxysmal nocturnal hemoglobinuria.
Using a “bottom-up” approach, researchers at the National Institutes of Health and in the United Kingdom identified 25 patients with somatic UBA1 mutations and noticed that they had strikingly similar autoinflammatory syndromes. UBA1 encodes ubiquitin E1, which is part of the pathway the breaks down proteins as part of the normal cellular machine. It is localized to the X chromosome, so all 25 affected patients were males, and most were aged between 40 and 70 years. These patients had an autoinflammatory syndrome characterized by fever, chondritis (similar to relapsing polychondritis), vasculitis, and neutrophilic dermatoses. Many patients also had features of myelodysplastic syndrome and plasma cell dyscrasia. The inflammatory pattern in this condition seems to show elevations in tumor necrosis factor, interleukin-6, and interferon-gamma.
So why is this syndrome relevant to dermatology? We are often asked to evaluate patients for neutrophilic dermatosis and vasculitis, and many affected patients had clinical and histologic findings compatible with polyarteritis nodosa and Sweet syndrome. When confronted with a neutrophilic dermatosis, we’ve all been taught to evaluate for myelodysplastic syndrome, which many of these patients appeared to have, at least on the surface. When bone marrow biopsies were done, the myeloid cell precursors that give rise to neutrophils were noted to have prominent cytoplasmic vacuoles, hence the “V” in VEXAS.
In reading the article describing 25 patients with this syndrome, which was published in the New England Journal of Medicine, I was struck by how refractory they were to treatment. Most patients had been treated with systemic steroids, multiple biologics, and several nonbiologic medications that are mainstays of treatment for neutrophilic dermatosis like dapsone and colchicine. I was fortunate enough to speak to Amanda Ombrello, MD, of the National Human Genome Research Institute, one of the lead authors of the paper, who drew my attention to the supplementary appendix, which showed the marked injection-site reactions some patients had to anakinra – yet another reason why a patient might end up in a dermatology clinic. In my mind, all of these features could be a clue to a diagnosis of VEXAS syndrome.
Many patients seemed to fare poorly, with 40% of patients dying before the completion of the study. When it comes to extremely rare diseases, it seems that the more physicians who are aware of the existence of a particular syndrome, the more likely it is a patient will come under our care and be correctly diagnosed.
Dr. Saardi is a dermatologist and internist, and is director of the inpatient dermatology service at the George Washington University Hospital, Washington. He has no disclosures.
Study shows potential of remote Parkinson’s disease genotyping
according to a pilot study sponsored by the Parkinson’s Foundation.
“Overall we found high levels of participant satisfaction with Parkinson’s testing and genetic counseling and no significant difference in outcomes concerning satisfaction, knowledge, and impact of genetic testing between disclosure of results and genetic counseling in-person by either a neurologist or a genetic counselor or via telephone by a remove genetic counselor at a centralized center,” said Jennifer L. Verbrugge, MS, a genetic counselor at Indiana University, Indianapolis, in reporting results of the PD GENEration pilot study, presented at the 2021 annual meeting of the American Academy of Neurology.
COVID complication
The study launched in the summer of 2019 with the goal of enrolling 600 participants. However, because of the COVID-19 pandemic, enrollment was truncated. The pilot study eventually enrolled 289 patients, 205 of whom returned their postgenetic counseling surveys, Ms. Verbrugge said. The pilot study goal was to evaluate the feasibility and impact of in-person versus remote genetic testing and counseling for people with Parkinson’s disease.
“The study hopes to reach its ultimate goal, which is to deliver Parkinson’s disease–related genetic testing and counseling to upward of 15,000 people with Parkinson’s,” Ms. Verbrugge said. The program is also planning to expand to include Spanish speakers.
In the pilot study, genetic results were positive in 17% of patients, with 15% (n = 42) having positive heterozygous variants and 8% having variants of uncertain significance. “We did not see significant differences in these outcomes when we compared the mode and genetic counselors involved,” Ms. Verbrugge said.
The study did find that in-person testing and counseling “was associated with increased participant feelings that they were partners in care,” Ms. Verbrugge added. “This is something we are going to continue to evaluate as time goes on.”
However, as the COVID-19 pandemic pushed clinicians to develop virtual platforms, it resulted in a function through which participants can complete all genetic study activities remotely, she said. The study organizers anticipate that as pandemic restrictions ease, they will be able to reach their original goal of 600 participants along with those recruited in an expansion phase.
“As restrictions related to the pandemic ease, we anticipate that more Parkinson’s disease gene-targeted clinical trials will emerge, with aims to recruit people who carry certain gene variants,” Ms. Verbrugge said in an interview. “Many people with Parkinson’s disease may therefore benefit from genetic testing and learning if they carry a Parkinson’s disease related gene variant from participation in the PD GENEration study.”
Increasing patient access
To scale up to the 15,000-population goal for the program, PD GENEration has launched a new protocol designed to increase patient access at new study sites, Ms. Verbrugge said. “This protocol includes an abbreviate version of the clinical data collected, while it maintains the critical component of genetic counseling in the testing process.”
Going forward, the PD GENEration study will focus on improving access to genetic testing and counseling in underrepresented and rural populations, Ms. Verbrugge said. “These efforts will also generate valuable genomic data, allowing researchers to learn more about the causes of Parkinson’s disease in diverse and underrepresented populations. The study will be expanding research efforts concerning the genomic data to gain insights about the seven key genes studied as well as new genes linked to Parkinson’s disease.”
The work of the PD GENEration study is timely, said David K. Simon, MD, PhD, of Harvard Medical School and director of the Parkinson’s Disease & Movement Disorders Center at Beth Israel Deaconess Medical Center, both in Boston. “This is very important to identify such patients now, as clinical trials targeting people with specific genetic mutations or variants are coming soon, and in some cases already are underway. The feasibility and speed of enrollment for those trials will be greatly facilitate if we know in advance who are the people with Parkinson’s disease who have mutations that would make them eligible for the particular trials.”
The fact that the study provides free genetic testing to people with Parkinson’s disease isn’t to be overlooked. “This was an important study to address the question of whether or not remote genetic counseling was feasible and effective, and the results are meaningful given the randomized prospective design,” Dr. Simon said.
Ms. Verbrugge has no relevant relationships to disclose. Dr. Simon reports receiving research funding from the Parkinson’s Foundation.
according to a pilot study sponsored by the Parkinson’s Foundation.
“Overall we found high levels of participant satisfaction with Parkinson’s testing and genetic counseling and no significant difference in outcomes concerning satisfaction, knowledge, and impact of genetic testing between disclosure of results and genetic counseling in-person by either a neurologist or a genetic counselor or via telephone by a remove genetic counselor at a centralized center,” said Jennifer L. Verbrugge, MS, a genetic counselor at Indiana University, Indianapolis, in reporting results of the PD GENEration pilot study, presented at the 2021 annual meeting of the American Academy of Neurology.
COVID complication
The study launched in the summer of 2019 with the goal of enrolling 600 participants. However, because of the COVID-19 pandemic, enrollment was truncated. The pilot study eventually enrolled 289 patients, 205 of whom returned their postgenetic counseling surveys, Ms. Verbrugge said. The pilot study goal was to evaluate the feasibility and impact of in-person versus remote genetic testing and counseling for people with Parkinson’s disease.
“The study hopes to reach its ultimate goal, which is to deliver Parkinson’s disease–related genetic testing and counseling to upward of 15,000 people with Parkinson’s,” Ms. Verbrugge said. The program is also planning to expand to include Spanish speakers.
In the pilot study, genetic results were positive in 17% of patients, with 15% (n = 42) having positive heterozygous variants and 8% having variants of uncertain significance. “We did not see significant differences in these outcomes when we compared the mode and genetic counselors involved,” Ms. Verbrugge said.
The study did find that in-person testing and counseling “was associated with increased participant feelings that they were partners in care,” Ms. Verbrugge added. “This is something we are going to continue to evaluate as time goes on.”
However, as the COVID-19 pandemic pushed clinicians to develop virtual platforms, it resulted in a function through which participants can complete all genetic study activities remotely, she said. The study organizers anticipate that as pandemic restrictions ease, they will be able to reach their original goal of 600 participants along with those recruited in an expansion phase.
“As restrictions related to the pandemic ease, we anticipate that more Parkinson’s disease gene-targeted clinical trials will emerge, with aims to recruit people who carry certain gene variants,” Ms. Verbrugge said in an interview. “Many people with Parkinson’s disease may therefore benefit from genetic testing and learning if they carry a Parkinson’s disease related gene variant from participation in the PD GENEration study.”
Increasing patient access
To scale up to the 15,000-population goal for the program, PD GENEration has launched a new protocol designed to increase patient access at new study sites, Ms. Verbrugge said. “This protocol includes an abbreviate version of the clinical data collected, while it maintains the critical component of genetic counseling in the testing process.”
Going forward, the PD GENEration study will focus on improving access to genetic testing and counseling in underrepresented and rural populations, Ms. Verbrugge said. “These efforts will also generate valuable genomic data, allowing researchers to learn more about the causes of Parkinson’s disease in diverse and underrepresented populations. The study will be expanding research efforts concerning the genomic data to gain insights about the seven key genes studied as well as new genes linked to Parkinson’s disease.”
The work of the PD GENEration study is timely, said David K. Simon, MD, PhD, of Harvard Medical School and director of the Parkinson’s Disease & Movement Disorders Center at Beth Israel Deaconess Medical Center, both in Boston. “This is very important to identify such patients now, as clinical trials targeting people with specific genetic mutations or variants are coming soon, and in some cases already are underway. The feasibility and speed of enrollment for those trials will be greatly facilitate if we know in advance who are the people with Parkinson’s disease who have mutations that would make them eligible for the particular trials.”
The fact that the study provides free genetic testing to people with Parkinson’s disease isn’t to be overlooked. “This was an important study to address the question of whether or not remote genetic counseling was feasible and effective, and the results are meaningful given the randomized prospective design,” Dr. Simon said.
Ms. Verbrugge has no relevant relationships to disclose. Dr. Simon reports receiving research funding from the Parkinson’s Foundation.
according to a pilot study sponsored by the Parkinson’s Foundation.
“Overall we found high levels of participant satisfaction with Parkinson’s testing and genetic counseling and no significant difference in outcomes concerning satisfaction, knowledge, and impact of genetic testing between disclosure of results and genetic counseling in-person by either a neurologist or a genetic counselor or via telephone by a remove genetic counselor at a centralized center,” said Jennifer L. Verbrugge, MS, a genetic counselor at Indiana University, Indianapolis, in reporting results of the PD GENEration pilot study, presented at the 2021 annual meeting of the American Academy of Neurology.
COVID complication
The study launched in the summer of 2019 with the goal of enrolling 600 participants. However, because of the COVID-19 pandemic, enrollment was truncated. The pilot study eventually enrolled 289 patients, 205 of whom returned their postgenetic counseling surveys, Ms. Verbrugge said. The pilot study goal was to evaluate the feasibility and impact of in-person versus remote genetic testing and counseling for people with Parkinson’s disease.
“The study hopes to reach its ultimate goal, which is to deliver Parkinson’s disease–related genetic testing and counseling to upward of 15,000 people with Parkinson’s,” Ms. Verbrugge said. The program is also planning to expand to include Spanish speakers.
In the pilot study, genetic results were positive in 17% of patients, with 15% (n = 42) having positive heterozygous variants and 8% having variants of uncertain significance. “We did not see significant differences in these outcomes when we compared the mode and genetic counselors involved,” Ms. Verbrugge said.
The study did find that in-person testing and counseling “was associated with increased participant feelings that they were partners in care,” Ms. Verbrugge added. “This is something we are going to continue to evaluate as time goes on.”
However, as the COVID-19 pandemic pushed clinicians to develop virtual platforms, it resulted in a function through which participants can complete all genetic study activities remotely, she said. The study organizers anticipate that as pandemic restrictions ease, they will be able to reach their original goal of 600 participants along with those recruited in an expansion phase.
“As restrictions related to the pandemic ease, we anticipate that more Parkinson’s disease gene-targeted clinical trials will emerge, with aims to recruit people who carry certain gene variants,” Ms. Verbrugge said in an interview. “Many people with Parkinson’s disease may therefore benefit from genetic testing and learning if they carry a Parkinson’s disease related gene variant from participation in the PD GENEration study.”
Increasing patient access
To scale up to the 15,000-population goal for the program, PD GENEration has launched a new protocol designed to increase patient access at new study sites, Ms. Verbrugge said. “This protocol includes an abbreviate version of the clinical data collected, while it maintains the critical component of genetic counseling in the testing process.”
Going forward, the PD GENEration study will focus on improving access to genetic testing and counseling in underrepresented and rural populations, Ms. Verbrugge said. “These efforts will also generate valuable genomic data, allowing researchers to learn more about the causes of Parkinson’s disease in diverse and underrepresented populations. The study will be expanding research efforts concerning the genomic data to gain insights about the seven key genes studied as well as new genes linked to Parkinson’s disease.”
The work of the PD GENEration study is timely, said David K. Simon, MD, PhD, of Harvard Medical School and director of the Parkinson’s Disease & Movement Disorders Center at Beth Israel Deaconess Medical Center, both in Boston. “This is very important to identify such patients now, as clinical trials targeting people with specific genetic mutations or variants are coming soon, and in some cases already are underway. The feasibility and speed of enrollment for those trials will be greatly facilitate if we know in advance who are the people with Parkinson’s disease who have mutations that would make them eligible for the particular trials.”
The fact that the study provides free genetic testing to people with Parkinson’s disease isn’t to be overlooked. “This was an important study to address the question of whether or not remote genetic counseling was feasible and effective, and the results are meaningful given the randomized prospective design,” Dr. Simon said.
Ms. Verbrugge has no relevant relationships to disclose. Dr. Simon reports receiving research funding from the Parkinson’s Foundation.
FROM AAN 2021
The ripple effect
“I want my life to mean something.”
She was young, energetic, and idealistic. She was seeing me for her migraines, but our conversation had turned to her applying for medical school.
“I want my life to mean something.”
I reflected on that later. I once said similar things, but now found myself wondering, two-thirds of the way through my career, did it?
The world certainly isn’t safer, geopolitically or environmentally, now than it was when I left medical school. Hell, the idea that there’d actually be another worldwide pandemic was pretty much beyond me then. That seemed so 1918.
I can’t even say I’ve made a huge difference in medicine. I’m not on the front line of research, inventing cures and tests that will change what we do.
I’m certainly far removed from the front lines of the pandemic.
But realistically, none of those things were ever really my goal, either.
“I want my life to mean something.”
Sometimes it’s hard to think I’ve made a difference. Day in and day out I’m at my office, quietly sitting behind a desk and trying to look smart. For all good intentions ... at some point it’s just a job.
Then I realized that the job isn’t about me. It’s about her, and the many other people who come to me for help. The real meaning is the impact on their lives.
Anytime we see a patient and make their lives better, either through treatment or compassion, it creates a ripple effect. It helps their family, friends, and coworkers. Whether we’re actually giving help or just understanding.
It might even inspire one of them to go into medicine, because my generation will be drifting toward retirement in the next 10 years.
Our care may set off a chain reaction we can’t see. Perhaps the patient you help will return to work and initiate some action that will bring a marked benefit to us all. Or someone in their circle, freed or inspired by their improvement, will bring about such a change.
And that’s meaning enough for me.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“I want my life to mean something.”
She was young, energetic, and idealistic. She was seeing me for her migraines, but our conversation had turned to her applying for medical school.
“I want my life to mean something.”
I reflected on that later. I once said similar things, but now found myself wondering, two-thirds of the way through my career, did it?
The world certainly isn’t safer, geopolitically or environmentally, now than it was when I left medical school. Hell, the idea that there’d actually be another worldwide pandemic was pretty much beyond me then. That seemed so 1918.
I can’t even say I’ve made a huge difference in medicine. I’m not on the front line of research, inventing cures and tests that will change what we do.
I’m certainly far removed from the front lines of the pandemic.
But realistically, none of those things were ever really my goal, either.
“I want my life to mean something.”
Sometimes it’s hard to think I’ve made a difference. Day in and day out I’m at my office, quietly sitting behind a desk and trying to look smart. For all good intentions ... at some point it’s just a job.
Then I realized that the job isn’t about me. It’s about her, and the many other people who come to me for help. The real meaning is the impact on their lives.
Anytime we see a patient and make their lives better, either through treatment or compassion, it creates a ripple effect. It helps their family, friends, and coworkers. Whether we’re actually giving help or just understanding.
It might even inspire one of them to go into medicine, because my generation will be drifting toward retirement in the next 10 years.
Our care may set off a chain reaction we can’t see. Perhaps the patient you help will return to work and initiate some action that will bring a marked benefit to us all. Or someone in their circle, freed or inspired by their improvement, will bring about such a change.
And that’s meaning enough for me.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“I want my life to mean something.”
She was young, energetic, and idealistic. She was seeing me for her migraines, but our conversation had turned to her applying for medical school.
“I want my life to mean something.”
I reflected on that later. I once said similar things, but now found myself wondering, two-thirds of the way through my career, did it?
The world certainly isn’t safer, geopolitically or environmentally, now than it was when I left medical school. Hell, the idea that there’d actually be another worldwide pandemic was pretty much beyond me then. That seemed so 1918.
I can’t even say I’ve made a huge difference in medicine. I’m not on the front line of research, inventing cures and tests that will change what we do.
I’m certainly far removed from the front lines of the pandemic.
But realistically, none of those things were ever really my goal, either.
“I want my life to mean something.”
Sometimes it’s hard to think I’ve made a difference. Day in and day out I’m at my office, quietly sitting behind a desk and trying to look smart. For all good intentions ... at some point it’s just a job.
Then I realized that the job isn’t about me. It’s about her, and the many other people who come to me for help. The real meaning is the impact on their lives.
Anytime we see a patient and make their lives better, either through treatment or compassion, it creates a ripple effect. It helps their family, friends, and coworkers. Whether we’re actually giving help or just understanding.
It might even inspire one of them to go into medicine, because my generation will be drifting toward retirement in the next 10 years.
Our care may set off a chain reaction we can’t see. Perhaps the patient you help will return to work and initiate some action that will bring a marked benefit to us all. Or someone in their circle, freed or inspired by their improvement, will bring about such a change.
And that’s meaning enough for me.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Rimegepant looks safe in migraine patients with cardiovascular risk
Results from a 1-year, open-label safety study suggest that Patients who fall into this category may be ineligible for treatment with triptans.
There are mechanistic concerns with rimegepant and related CGRP receptor antagonists. They block CGRP’s effect in the central nervous system, but CGRP is also active in blood vessels and the heart, leading to the possibility that countering its vasodilating effect could expose organs to risk of ischemia.
The Food and Drug Administration approved rimegepant in 2020 for treatment of acute migraine attacks. Sponsor Biohaven is also seeking approval for migraine prevention after a successful phase 3 study published January 2021 in The Lancet.
Susan Hutchinson, MD, who is a headache specialist at Orange County Migraine & Headache Center in Irvine, Calif., presented the results at the American Academy of Neurology’s 2021 annual meeting. The open-label study suggested that rimegepant is generally safe. “The proportion of subjects reporting at least one adverse event was similar among subjects whether they had zero, one, or two or more cardiovascular disease risk factors, and also among those with low and moderate to high 10-year cardiovascular risk, as determined by the Framingham Risk Score,” said Dr. Hutchinson during her presentation.
Still, there was one concerning case: A 53-year-old man experienced an attack of angina. But he already had angina prior to the study, was being treated for hypercholesterolemia, and had current or former exposure to statins. “This adverse event was deemed by the investigator to not be related to rimegepant,” said Dr. Hutchinson.
During the following question-and-answer session, an attendee pressed Dr. Hutchinson about the case, and she admitted to some initial doubts. “That was my concern when I saw those slides. I’m like, ‘oh, my goodness.’ ” She clarified that the man’s angina history dated to 2016, which was several years before the trial, and the episode of angina occurred 7 months after the first dose of rimegepant. “He was treated with nitroglycerin and taken out of the trial,” said Dr. Hutchinson.
Proper patient selection is key
The research adds to the literature on rimegepant by providing data on multiple uses, as opposed to the phase 3 study, which only looked at single use, according to Olivia Begasse de Dhaem, MD, who is a neurology attending physician at Stamford (Conn.) Health and was the session moderator. Rimegepant and other oral CGRP receptor antagonists, including the FDA-approved ubrogepant and the investigative drug atogepant, will help fill the gap of patients who don’t tolerate or are ineligible for triptans, she said.
Dr. Begasse de Dhaem pointed out that patient selection remains important. “I think the main thing for patient care is to look at whether the patient we are treating would fit within the inclusion criteria, or would have been excluded from this study,” said Dr. Begasse de Dhaem. Specifically, according to its clinicaltrials.gov page, the trial excluded patients with hemiplegic and basilar migraine, as well as patients with uncontrolled, unstable, or recently diagnosed cardiovascular disease, those with a body mass index of 30 kg/m2 or higher, and hemoglobin A1c levels of 6.5% or higher. “This also looked at people with less than 15 migraine days per month, so it’s limited in how much we can extrapolate to people with chronic migraine who may take more than 7.7 rimegepant [doses, the mean value taken by trial participants] per month,” Dr. Begasse de Dhaem added.
She also applauded the inclusion of older patients in the study, noting that most migraine studies have an upper age limit.
The study included subjects who experienced 2-14 moderate or severe migraine attacks per month, and they were allowed to take other migraine medications. Cardiovascular risk factors did not prevent entry to the trial and, like the previous pivotal trial, the long-term safety study admitted subjects older than 65. Among the study cohort, 1,514 participants were told to treat migraine pain of any intensity with 75 mg rimegepant up to once per day on an as-needed basis (PRN), and a second group of 286 were told to take 75 mg rimegepant every other day for 12 weeks, along with PRN dosing on nonscheduled treatment days.
Nearly 90% of subjects were female, the mean age was 43.1 years, and 3.7% were age 65 or older. Among the study participants, 40.8% had cardiovascular risk factors, including 28.8% with one risk factor, and 12.1% with two or more. About 7% had a moderate to high (≥10%) 10-year cardiovascular risk by Framingham Risk Score, 23.6% had a family history of coronary artery disease, 11.7% were being treated for hypertension, 10.4% smoked, 8.3% were being treated with a statin, and 3.0% had a history of diabetes.
In total, subjects were exposed to 112,014 doses of rimegepant, a mean of 7.7 doses per 4-week period. The exposure was similar across all risk groups, which included zero risk factors, one risk factor, and two or more risk factors; FRS of less than 10%; and FRS of 10% or greater. The most common adverse events were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%). The frequency of one or more adverse events was similar among those with zero cardiovascular risk factors (59.6%), one risk factor (61.4%), two or more risk factors (62.2%), FRS less than 10% (59.9%), and FRS of 10% or greater (59.9%).
The study was funded by Biohaven Pharmaceuticals. Dr. Hutchinson has been a consultant or advisory board member for Biohaven, Alder, Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. She has been on the speaker’s bureau for Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. Dr. Begasse de Dhaem has no relevant financial disclosures.
Results from a 1-year, open-label safety study suggest that Patients who fall into this category may be ineligible for treatment with triptans.
There are mechanistic concerns with rimegepant and related CGRP receptor antagonists. They block CGRP’s effect in the central nervous system, but CGRP is also active in blood vessels and the heart, leading to the possibility that countering its vasodilating effect could expose organs to risk of ischemia.
The Food and Drug Administration approved rimegepant in 2020 for treatment of acute migraine attacks. Sponsor Biohaven is also seeking approval for migraine prevention after a successful phase 3 study published January 2021 in The Lancet.
Susan Hutchinson, MD, who is a headache specialist at Orange County Migraine & Headache Center in Irvine, Calif., presented the results at the American Academy of Neurology’s 2021 annual meeting. The open-label study suggested that rimegepant is generally safe. “The proportion of subjects reporting at least one adverse event was similar among subjects whether they had zero, one, or two or more cardiovascular disease risk factors, and also among those with low and moderate to high 10-year cardiovascular risk, as determined by the Framingham Risk Score,” said Dr. Hutchinson during her presentation.
Still, there was one concerning case: A 53-year-old man experienced an attack of angina. But he already had angina prior to the study, was being treated for hypercholesterolemia, and had current or former exposure to statins. “This adverse event was deemed by the investigator to not be related to rimegepant,” said Dr. Hutchinson.
During the following question-and-answer session, an attendee pressed Dr. Hutchinson about the case, and she admitted to some initial doubts. “That was my concern when I saw those slides. I’m like, ‘oh, my goodness.’ ” She clarified that the man’s angina history dated to 2016, which was several years before the trial, and the episode of angina occurred 7 months after the first dose of rimegepant. “He was treated with nitroglycerin and taken out of the trial,” said Dr. Hutchinson.
Proper patient selection is key
The research adds to the literature on rimegepant by providing data on multiple uses, as opposed to the phase 3 study, which only looked at single use, according to Olivia Begasse de Dhaem, MD, who is a neurology attending physician at Stamford (Conn.) Health and was the session moderator. Rimegepant and other oral CGRP receptor antagonists, including the FDA-approved ubrogepant and the investigative drug atogepant, will help fill the gap of patients who don’t tolerate or are ineligible for triptans, she said.
Dr. Begasse de Dhaem pointed out that patient selection remains important. “I think the main thing for patient care is to look at whether the patient we are treating would fit within the inclusion criteria, or would have been excluded from this study,” said Dr. Begasse de Dhaem. Specifically, according to its clinicaltrials.gov page, the trial excluded patients with hemiplegic and basilar migraine, as well as patients with uncontrolled, unstable, or recently diagnosed cardiovascular disease, those with a body mass index of 30 kg/m2 or higher, and hemoglobin A1c levels of 6.5% or higher. “This also looked at people with less than 15 migraine days per month, so it’s limited in how much we can extrapolate to people with chronic migraine who may take more than 7.7 rimegepant [doses, the mean value taken by trial participants] per month,” Dr. Begasse de Dhaem added.
She also applauded the inclusion of older patients in the study, noting that most migraine studies have an upper age limit.
The study included subjects who experienced 2-14 moderate or severe migraine attacks per month, and they were allowed to take other migraine medications. Cardiovascular risk factors did not prevent entry to the trial and, like the previous pivotal trial, the long-term safety study admitted subjects older than 65. Among the study cohort, 1,514 participants were told to treat migraine pain of any intensity with 75 mg rimegepant up to once per day on an as-needed basis (PRN), and a second group of 286 were told to take 75 mg rimegepant every other day for 12 weeks, along with PRN dosing on nonscheduled treatment days.
Nearly 90% of subjects were female, the mean age was 43.1 years, and 3.7% were age 65 or older. Among the study participants, 40.8% had cardiovascular risk factors, including 28.8% with one risk factor, and 12.1% with two or more. About 7% had a moderate to high (≥10%) 10-year cardiovascular risk by Framingham Risk Score, 23.6% had a family history of coronary artery disease, 11.7% were being treated for hypertension, 10.4% smoked, 8.3% were being treated with a statin, and 3.0% had a history of diabetes.
In total, subjects were exposed to 112,014 doses of rimegepant, a mean of 7.7 doses per 4-week period. The exposure was similar across all risk groups, which included zero risk factors, one risk factor, and two or more risk factors; FRS of less than 10%; and FRS of 10% or greater. The most common adverse events were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%). The frequency of one or more adverse events was similar among those with zero cardiovascular risk factors (59.6%), one risk factor (61.4%), two or more risk factors (62.2%), FRS less than 10% (59.9%), and FRS of 10% or greater (59.9%).
The study was funded by Biohaven Pharmaceuticals. Dr. Hutchinson has been a consultant or advisory board member for Biohaven, Alder, Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. She has been on the speaker’s bureau for Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. Dr. Begasse de Dhaem has no relevant financial disclosures.
Results from a 1-year, open-label safety study suggest that Patients who fall into this category may be ineligible for treatment with triptans.
There are mechanistic concerns with rimegepant and related CGRP receptor antagonists. They block CGRP’s effect in the central nervous system, but CGRP is also active in blood vessels and the heart, leading to the possibility that countering its vasodilating effect could expose organs to risk of ischemia.
The Food and Drug Administration approved rimegepant in 2020 for treatment of acute migraine attacks. Sponsor Biohaven is also seeking approval for migraine prevention after a successful phase 3 study published January 2021 in The Lancet.
Susan Hutchinson, MD, who is a headache specialist at Orange County Migraine & Headache Center in Irvine, Calif., presented the results at the American Academy of Neurology’s 2021 annual meeting. The open-label study suggested that rimegepant is generally safe. “The proportion of subjects reporting at least one adverse event was similar among subjects whether they had zero, one, or two or more cardiovascular disease risk factors, and also among those with low and moderate to high 10-year cardiovascular risk, as determined by the Framingham Risk Score,” said Dr. Hutchinson during her presentation.
Still, there was one concerning case: A 53-year-old man experienced an attack of angina. But he already had angina prior to the study, was being treated for hypercholesterolemia, and had current or former exposure to statins. “This adverse event was deemed by the investigator to not be related to rimegepant,” said Dr. Hutchinson.
During the following question-and-answer session, an attendee pressed Dr. Hutchinson about the case, and she admitted to some initial doubts. “That was my concern when I saw those slides. I’m like, ‘oh, my goodness.’ ” She clarified that the man’s angina history dated to 2016, which was several years before the trial, and the episode of angina occurred 7 months after the first dose of rimegepant. “He was treated with nitroglycerin and taken out of the trial,” said Dr. Hutchinson.
Proper patient selection is key
The research adds to the literature on rimegepant by providing data on multiple uses, as opposed to the phase 3 study, which only looked at single use, according to Olivia Begasse de Dhaem, MD, who is a neurology attending physician at Stamford (Conn.) Health and was the session moderator. Rimegepant and other oral CGRP receptor antagonists, including the FDA-approved ubrogepant and the investigative drug atogepant, will help fill the gap of patients who don’t tolerate or are ineligible for triptans, she said.
Dr. Begasse de Dhaem pointed out that patient selection remains important. “I think the main thing for patient care is to look at whether the patient we are treating would fit within the inclusion criteria, or would have been excluded from this study,” said Dr. Begasse de Dhaem. Specifically, according to its clinicaltrials.gov page, the trial excluded patients with hemiplegic and basilar migraine, as well as patients with uncontrolled, unstable, or recently diagnosed cardiovascular disease, those with a body mass index of 30 kg/m2 or higher, and hemoglobin A1c levels of 6.5% or higher. “This also looked at people with less than 15 migraine days per month, so it’s limited in how much we can extrapolate to people with chronic migraine who may take more than 7.7 rimegepant [doses, the mean value taken by trial participants] per month,” Dr. Begasse de Dhaem added.
She also applauded the inclusion of older patients in the study, noting that most migraine studies have an upper age limit.
The study included subjects who experienced 2-14 moderate or severe migraine attacks per month, and they were allowed to take other migraine medications. Cardiovascular risk factors did not prevent entry to the trial and, like the previous pivotal trial, the long-term safety study admitted subjects older than 65. Among the study cohort, 1,514 participants were told to treat migraine pain of any intensity with 75 mg rimegepant up to once per day on an as-needed basis (PRN), and a second group of 286 were told to take 75 mg rimegepant every other day for 12 weeks, along with PRN dosing on nonscheduled treatment days.
Nearly 90% of subjects were female, the mean age was 43.1 years, and 3.7% were age 65 or older. Among the study participants, 40.8% had cardiovascular risk factors, including 28.8% with one risk factor, and 12.1% with two or more. About 7% had a moderate to high (≥10%) 10-year cardiovascular risk by Framingham Risk Score, 23.6% had a family history of coronary artery disease, 11.7% were being treated for hypertension, 10.4% smoked, 8.3% were being treated with a statin, and 3.0% had a history of diabetes.
In total, subjects were exposed to 112,014 doses of rimegepant, a mean of 7.7 doses per 4-week period. The exposure was similar across all risk groups, which included zero risk factors, one risk factor, and two or more risk factors; FRS of less than 10%; and FRS of 10% or greater. The most common adverse events were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%). The frequency of one or more adverse events was similar among those with zero cardiovascular risk factors (59.6%), one risk factor (61.4%), two or more risk factors (62.2%), FRS less than 10% (59.9%), and FRS of 10% or greater (59.9%).
The study was funded by Biohaven Pharmaceuticals. Dr. Hutchinson has been a consultant or advisory board member for Biohaven, Alder, Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. She has been on the speaker’s bureau for Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. Dr. Begasse de Dhaem has no relevant financial disclosures.
FROM AAN 2021
Do ObGyns plan on getting a 9vHPV vaccine?
In his editorial, "9vHPV vaccine: Prevention of oropharyngeal cancer" (November 2020), Editor in Chief Robert L. Barbieri, MD, asked, "As a gynecologist, should you receive the 9vHPV vaccine?" He noted that the American Society for Colposcopy and Cervical Pathology (ASCCP) now recommends that clinicians "who are routinely exposed to HPVs consider 9vHPV vaccination" and cited a study that found that 19% of 700 gynecologists who performed LEEP procedures without a surgical mask had HPV DNA present in the nose (which was no longer detectable at 24 months). OBG MANAGEMENT followed up with a poll for readers to ask, "will you get the [9vHPV] vaccine?" based on the new ASCCP recommendations.
A total of 157 readers cast their vote:
55% (86 readers) said yes
19% (30 readers) said no
26% (41 readers) were undecided
In his editorial, "9vHPV vaccine: Prevention of oropharyngeal cancer" (November 2020), Editor in Chief Robert L. Barbieri, MD, asked, "As a gynecologist, should you receive the 9vHPV vaccine?" He noted that the American Society for Colposcopy and Cervical Pathology (ASCCP) now recommends that clinicians "who are routinely exposed to HPVs consider 9vHPV vaccination" and cited a study that found that 19% of 700 gynecologists who performed LEEP procedures without a surgical mask had HPV DNA present in the nose (which was no longer detectable at 24 months). OBG MANAGEMENT followed up with a poll for readers to ask, "will you get the [9vHPV] vaccine?" based on the new ASCCP recommendations.
A total of 157 readers cast their vote:
55% (86 readers) said yes
19% (30 readers) said no
26% (41 readers) were undecided
In his editorial, "9vHPV vaccine: Prevention of oropharyngeal cancer" (November 2020), Editor in Chief Robert L. Barbieri, MD, asked, "As a gynecologist, should you receive the 9vHPV vaccine?" He noted that the American Society for Colposcopy and Cervical Pathology (ASCCP) now recommends that clinicians "who are routinely exposed to HPVs consider 9vHPV vaccination" and cited a study that found that 19% of 700 gynecologists who performed LEEP procedures without a surgical mask had HPV DNA present in the nose (which was no longer detectable at 24 months). OBG MANAGEMENT followed up with a poll for readers to ask, "will you get the [9vHPV] vaccine?" based on the new ASCCP recommendations.
A total of 157 readers cast their vote:
55% (86 readers) said yes
19% (30 readers) said no
26% (41 readers) were undecided
Dr. G. Gayle Stephens was a teacher, progressive force, and ‘poet laureate of family medicine’
G. Gayle Stephens, MD, who is roundly regarded as one of the founders of family medicine, gave his talk “Family Medicine as Counterculture” at the Society of Teachers of Family Medicine annual conference in 1979, 10 years after the specialty’s establishment.
The speech was then published, republished 10 years later, and, like many of Dr. Stephen’s other essays and articles, remains very much alive in the minds of practicing family physicians, in the teachings of FP academicians, and in the Google searches of budding FPs.
The late Dr. Stephens saw family medicine as a counterculture within medicine, rooted in social change. In his speech he examined these roots – in reform initiatives in the 1960s, and in certain philosophies and “minority” movements such as agrarianism and the preservation of rural life, utopianism, humanism, consumerism, and feminism.
He also looked forward, challenging the specialty to remain true to itself and its roots – to its belief in “uninhibited access” to medical care for everyone, for instance, and to continual whole-person and family-oriented care – and cautioned against moving to resemble the “rest of the medical bureaucracy.”
“Clearly we have been on the side of change in American life. We have identified ourselves with certain minorities and minority positions ... [and] been counter to many of the dominant forces in society,” Dr. Stephens said in his talk. Family practice “succeeded in the decade just past because we were identified with reforms that are more pervasive and powerful than ourselves.”
The family practice movement has “more in common with [the] counterculture than it does with the dominant scientific medical establishment,” he said.
A teacher and founder of medical education programs
Larry A. Green, MD, who was pursuing his own residency training as Dr. Stephens was leading a department of family practice, said
“It was from this philosophical position that he became a synthesizer and observer and interpreter of what was going on in the development of family medicine,” said Dr. Green, Distinguished Professor and Epperson Zorn Chair for Innovation in Family Medicine and Primary Care at the University of Colorado at Denver, Aurora.
Dr. Stephens, who died at home in 2014 at the age of 85, was “probably the most important person in exposing what I now consider to be a fact – that family medicine was the product of social changes ... of social movements related to women’s rights, civil rights, and social responsibility,” Dr. Green said. “He could recall lessons from the past and forecast the challenges of the future. And there was no one more effective in clarifying the importance of personal [doctor-patient] relationships in family medicine.”
After years of general practice in rural Wichita, Kan., his wife Eula Jean’s hometown, Dr. Stephens founded and led one of the first family medicine residencies at Wesley Hospital in Wichita in 1967. His core principles, as described on today’s Wesley Family Medicine Residency website, included that a family physician consider the whole person, be honest, have a full scope of training including behavioral and mental health, and be “reflective about him/herself ... [learning about] his/her assets, liabilities, foibles, and idiosyncrasies.” Dr. Stephens, who had grown up in rural Ashburn, Mo., later became the founding dean of the School of Primary Medical Care at the University of Alabama in Huntsville and then chaired the department of family practice at the University of Alabama at Birmingham.
A thought leader for family medicine
He held numerous state and national leadership positions, and initiated what became the Keystone Conference Series – an invitational gathering of leaders in family medicine that examined and discuss the specialty’s ongoing development. In 2006, he was elected to the Institute of Medicine of the National Academies of Science.
Dr. Stephens authored a textbook, The Intellectual Basis of Family Medicine (Tucson, Ariz.: Winter Publishing Company, 1982), and authored essays, which Dr. Green said will stand the test of time.
“Some of us refer to him as the poet laureate of family medicine,” Dr. Green noted.
In a 1974 article on clinical wisdom, Dr. Stephens wrote that “it is not enough to determine what condition the patient has, but also what patient has the condition.” In another of these essays, which was published in 1979, Dr. Stephens wrote that “physicians need to keep in touch with their own tradition and with public welfare if they are to be considered moral by the society that sponsors them, and from which they take their strength and privilege.”
These excerpts are featured in an article by John P. Geyman, MD, published in 2011 in Family Medicine, called “G. Gayle Stephens Festschrift”.
A ‘progressive force’
Linda Prine, MD, professor of family and community medicine at the Icahn School of Medicine at Mount Sinai, New York, knows of Dr. Stephens from her teachers. “The people I looked up to when I was a younger physician were quoting his Counterculture article,” she said.
“It’s not that I studied him. But whenever I heard someone speak about the values of family medicine, his name would come up [and] the values of universal health care and community care and putting the patients’ interests first ahead of the insurance companies and being a doctor for the whole family,” Dr. Prine said. Dr. Stephens was a “progressive force that our specialty has not always lived up to.”
Dr. Stephens voiced serious concerns about the impact of managed care in the 1980s and of “gatekeeping,” a practice intended to control access to specialists and reduce costs.
“He was many times not welcomed by family medicine [for his warnings] against the temptations that managed care presented,” said Dr. Green, the founding director of the Robert Graham Center, Washington. “He saw the conflict of interest of being a gatekeeper, how that would erode trust in a personal relationship with your personal doctor.”
“Gayle thought it was a disaster waiting to happen, and it was,” he said, referring to the eventual rejection by the public of barriers to direct access to specialists.
Through the 1990s and more recently, Dr. Stephens expressed frustration with the “medical-industrial complex” and the decline of family medicine after its surge in the 1970s and 1980s, Dr. Green said. “But in my opinion, near the end of his life, he was encouraged by young leaders who he saw grasped the important ideas from the ages.”
Dr. Stephens’ interest in medical education extended to nurses and nurse practitioners (the latter of whom had begun their discipline in the mid-1960s), and to optometrists, for whom he taught a recurring course in “physical diagnosis.”
A listener and proponent of listening
Linda Tompkins, RN, FNP, of Newton, Kan., trained with Dr. Stephens at part of a year-long nurse education program in the early 1970s at Wichita (Kan.) State University, where he was leading the department of family practice (prior to moving to Alabama). “You couldn’t ask too many questions,” she said. “And he never talked down to us, he wasn’t condescending. There were not a lot of doctors like that.”
Dr. Stephens spoke and wrote often about the importance of listening –about how it was vital to the “durable clinical relationship.” It was also vital to his writing and to his impact on the teachers of family medicine, said Dan Ostergaard, MD, who served as a residency director and in various staff leadership positions at the American Academy of Family Physicians, including in its division of education.
“He created a lot of aha moments for me, about where we came from and what we really need to be [as a specialty] and where we need to go,” said Dr. Ostergaard. “To be such a great thinker and a great writer, you have to be a great listener.”
“I can just visualize him,” he said, “leaning back in his chair while we were talking about residency criteria [or other issues], with a half-smile on his face and his reading glasses down his note, smoking his pipe and just looking at all of us, listening.”
Dr. Stephens’ papers are housed in the Center for the History of Family Medicine, a project of the AAFP Foundation.
G. Gayle Stephens, MD, who is roundly regarded as one of the founders of family medicine, gave his talk “Family Medicine as Counterculture” at the Society of Teachers of Family Medicine annual conference in 1979, 10 years after the specialty’s establishment.
The speech was then published, republished 10 years later, and, like many of Dr. Stephen’s other essays and articles, remains very much alive in the minds of practicing family physicians, in the teachings of FP academicians, and in the Google searches of budding FPs.
The late Dr. Stephens saw family medicine as a counterculture within medicine, rooted in social change. In his speech he examined these roots – in reform initiatives in the 1960s, and in certain philosophies and “minority” movements such as agrarianism and the preservation of rural life, utopianism, humanism, consumerism, and feminism.
He also looked forward, challenging the specialty to remain true to itself and its roots – to its belief in “uninhibited access” to medical care for everyone, for instance, and to continual whole-person and family-oriented care – and cautioned against moving to resemble the “rest of the medical bureaucracy.”
“Clearly we have been on the side of change in American life. We have identified ourselves with certain minorities and minority positions ... [and] been counter to many of the dominant forces in society,” Dr. Stephens said in his talk. Family practice “succeeded in the decade just past because we were identified with reforms that are more pervasive and powerful than ourselves.”
The family practice movement has “more in common with [the] counterculture than it does with the dominant scientific medical establishment,” he said.
A teacher and founder of medical education programs
Larry A. Green, MD, who was pursuing his own residency training as Dr. Stephens was leading a department of family practice, said
“It was from this philosophical position that he became a synthesizer and observer and interpreter of what was going on in the development of family medicine,” said Dr. Green, Distinguished Professor and Epperson Zorn Chair for Innovation in Family Medicine and Primary Care at the University of Colorado at Denver, Aurora.
Dr. Stephens, who died at home in 2014 at the age of 85, was “probably the most important person in exposing what I now consider to be a fact – that family medicine was the product of social changes ... of social movements related to women’s rights, civil rights, and social responsibility,” Dr. Green said. “He could recall lessons from the past and forecast the challenges of the future. And there was no one more effective in clarifying the importance of personal [doctor-patient] relationships in family medicine.”
After years of general practice in rural Wichita, Kan., his wife Eula Jean’s hometown, Dr. Stephens founded and led one of the first family medicine residencies at Wesley Hospital in Wichita in 1967. His core principles, as described on today’s Wesley Family Medicine Residency website, included that a family physician consider the whole person, be honest, have a full scope of training including behavioral and mental health, and be “reflective about him/herself ... [learning about] his/her assets, liabilities, foibles, and idiosyncrasies.” Dr. Stephens, who had grown up in rural Ashburn, Mo., later became the founding dean of the School of Primary Medical Care at the University of Alabama in Huntsville and then chaired the department of family practice at the University of Alabama at Birmingham.
A thought leader for family medicine
He held numerous state and national leadership positions, and initiated what became the Keystone Conference Series – an invitational gathering of leaders in family medicine that examined and discuss the specialty’s ongoing development. In 2006, he was elected to the Institute of Medicine of the National Academies of Science.
Dr. Stephens authored a textbook, The Intellectual Basis of Family Medicine (Tucson, Ariz.: Winter Publishing Company, 1982), and authored essays, which Dr. Green said will stand the test of time.
“Some of us refer to him as the poet laureate of family medicine,” Dr. Green noted.
In a 1974 article on clinical wisdom, Dr. Stephens wrote that “it is not enough to determine what condition the patient has, but also what patient has the condition.” In another of these essays, which was published in 1979, Dr. Stephens wrote that “physicians need to keep in touch with their own tradition and with public welfare if they are to be considered moral by the society that sponsors them, and from which they take their strength and privilege.”
These excerpts are featured in an article by John P. Geyman, MD, published in 2011 in Family Medicine, called “G. Gayle Stephens Festschrift”.
A ‘progressive force’
Linda Prine, MD, professor of family and community medicine at the Icahn School of Medicine at Mount Sinai, New York, knows of Dr. Stephens from her teachers. “The people I looked up to when I was a younger physician were quoting his Counterculture article,” she said.
“It’s not that I studied him. But whenever I heard someone speak about the values of family medicine, his name would come up [and] the values of universal health care and community care and putting the patients’ interests first ahead of the insurance companies and being a doctor for the whole family,” Dr. Prine said. Dr. Stephens was a “progressive force that our specialty has not always lived up to.”
Dr. Stephens voiced serious concerns about the impact of managed care in the 1980s and of “gatekeeping,” a practice intended to control access to specialists and reduce costs.
“He was many times not welcomed by family medicine [for his warnings] against the temptations that managed care presented,” said Dr. Green, the founding director of the Robert Graham Center, Washington. “He saw the conflict of interest of being a gatekeeper, how that would erode trust in a personal relationship with your personal doctor.”
“Gayle thought it was a disaster waiting to happen, and it was,” he said, referring to the eventual rejection by the public of barriers to direct access to specialists.
Through the 1990s and more recently, Dr. Stephens expressed frustration with the “medical-industrial complex” and the decline of family medicine after its surge in the 1970s and 1980s, Dr. Green said. “But in my opinion, near the end of his life, he was encouraged by young leaders who he saw grasped the important ideas from the ages.”
Dr. Stephens’ interest in medical education extended to nurses and nurse practitioners (the latter of whom had begun their discipline in the mid-1960s), and to optometrists, for whom he taught a recurring course in “physical diagnosis.”
A listener and proponent of listening
Linda Tompkins, RN, FNP, of Newton, Kan., trained with Dr. Stephens at part of a year-long nurse education program in the early 1970s at Wichita (Kan.) State University, where he was leading the department of family practice (prior to moving to Alabama). “You couldn’t ask too many questions,” she said. “And he never talked down to us, he wasn’t condescending. There were not a lot of doctors like that.”
Dr. Stephens spoke and wrote often about the importance of listening –about how it was vital to the “durable clinical relationship.” It was also vital to his writing and to his impact on the teachers of family medicine, said Dan Ostergaard, MD, who served as a residency director and in various staff leadership positions at the American Academy of Family Physicians, including in its division of education.
“He created a lot of aha moments for me, about where we came from and what we really need to be [as a specialty] and where we need to go,” said Dr. Ostergaard. “To be such a great thinker and a great writer, you have to be a great listener.”
“I can just visualize him,” he said, “leaning back in his chair while we were talking about residency criteria [or other issues], with a half-smile on his face and his reading glasses down his note, smoking his pipe and just looking at all of us, listening.”
Dr. Stephens’ papers are housed in the Center for the History of Family Medicine, a project of the AAFP Foundation.
G. Gayle Stephens, MD, who is roundly regarded as one of the founders of family medicine, gave his talk “Family Medicine as Counterculture” at the Society of Teachers of Family Medicine annual conference in 1979, 10 years after the specialty’s establishment.
The speech was then published, republished 10 years later, and, like many of Dr. Stephen’s other essays and articles, remains very much alive in the minds of practicing family physicians, in the teachings of FP academicians, and in the Google searches of budding FPs.
The late Dr. Stephens saw family medicine as a counterculture within medicine, rooted in social change. In his speech he examined these roots – in reform initiatives in the 1960s, and in certain philosophies and “minority” movements such as agrarianism and the preservation of rural life, utopianism, humanism, consumerism, and feminism.
He also looked forward, challenging the specialty to remain true to itself and its roots – to its belief in “uninhibited access” to medical care for everyone, for instance, and to continual whole-person and family-oriented care – and cautioned against moving to resemble the “rest of the medical bureaucracy.”
“Clearly we have been on the side of change in American life. We have identified ourselves with certain minorities and minority positions ... [and] been counter to many of the dominant forces in society,” Dr. Stephens said in his talk. Family practice “succeeded in the decade just past because we were identified with reforms that are more pervasive and powerful than ourselves.”
The family practice movement has “more in common with [the] counterculture than it does with the dominant scientific medical establishment,” he said.
A teacher and founder of medical education programs
Larry A. Green, MD, who was pursuing his own residency training as Dr. Stephens was leading a department of family practice, said
“It was from this philosophical position that he became a synthesizer and observer and interpreter of what was going on in the development of family medicine,” said Dr. Green, Distinguished Professor and Epperson Zorn Chair for Innovation in Family Medicine and Primary Care at the University of Colorado at Denver, Aurora.
Dr. Stephens, who died at home in 2014 at the age of 85, was “probably the most important person in exposing what I now consider to be a fact – that family medicine was the product of social changes ... of social movements related to women’s rights, civil rights, and social responsibility,” Dr. Green said. “He could recall lessons from the past and forecast the challenges of the future. And there was no one more effective in clarifying the importance of personal [doctor-patient] relationships in family medicine.”
After years of general practice in rural Wichita, Kan., his wife Eula Jean’s hometown, Dr. Stephens founded and led one of the first family medicine residencies at Wesley Hospital in Wichita in 1967. His core principles, as described on today’s Wesley Family Medicine Residency website, included that a family physician consider the whole person, be honest, have a full scope of training including behavioral and mental health, and be “reflective about him/herself ... [learning about] his/her assets, liabilities, foibles, and idiosyncrasies.” Dr. Stephens, who had grown up in rural Ashburn, Mo., later became the founding dean of the School of Primary Medical Care at the University of Alabama in Huntsville and then chaired the department of family practice at the University of Alabama at Birmingham.
A thought leader for family medicine
He held numerous state and national leadership positions, and initiated what became the Keystone Conference Series – an invitational gathering of leaders in family medicine that examined and discuss the specialty’s ongoing development. In 2006, he was elected to the Institute of Medicine of the National Academies of Science.
Dr. Stephens authored a textbook, The Intellectual Basis of Family Medicine (Tucson, Ariz.: Winter Publishing Company, 1982), and authored essays, which Dr. Green said will stand the test of time.
“Some of us refer to him as the poet laureate of family medicine,” Dr. Green noted.
In a 1974 article on clinical wisdom, Dr. Stephens wrote that “it is not enough to determine what condition the patient has, but also what patient has the condition.” In another of these essays, which was published in 1979, Dr. Stephens wrote that “physicians need to keep in touch with their own tradition and with public welfare if they are to be considered moral by the society that sponsors them, and from which they take their strength and privilege.”
These excerpts are featured in an article by John P. Geyman, MD, published in 2011 in Family Medicine, called “G. Gayle Stephens Festschrift”.
A ‘progressive force’
Linda Prine, MD, professor of family and community medicine at the Icahn School of Medicine at Mount Sinai, New York, knows of Dr. Stephens from her teachers. “The people I looked up to when I was a younger physician were quoting his Counterculture article,” she said.
“It’s not that I studied him. But whenever I heard someone speak about the values of family medicine, his name would come up [and] the values of universal health care and community care and putting the patients’ interests first ahead of the insurance companies and being a doctor for the whole family,” Dr. Prine said. Dr. Stephens was a “progressive force that our specialty has not always lived up to.”
Dr. Stephens voiced serious concerns about the impact of managed care in the 1980s and of “gatekeeping,” a practice intended to control access to specialists and reduce costs.
“He was many times not welcomed by family medicine [for his warnings] against the temptations that managed care presented,” said Dr. Green, the founding director of the Robert Graham Center, Washington. “He saw the conflict of interest of being a gatekeeper, how that would erode trust in a personal relationship with your personal doctor.”
“Gayle thought it was a disaster waiting to happen, and it was,” he said, referring to the eventual rejection by the public of barriers to direct access to specialists.
Through the 1990s and more recently, Dr. Stephens expressed frustration with the “medical-industrial complex” and the decline of family medicine after its surge in the 1970s and 1980s, Dr. Green said. “But in my opinion, near the end of his life, he was encouraged by young leaders who he saw grasped the important ideas from the ages.”
Dr. Stephens’ interest in medical education extended to nurses and nurse practitioners (the latter of whom had begun their discipline in the mid-1960s), and to optometrists, for whom he taught a recurring course in “physical diagnosis.”
A listener and proponent of listening
Linda Tompkins, RN, FNP, of Newton, Kan., trained with Dr. Stephens at part of a year-long nurse education program in the early 1970s at Wichita (Kan.) State University, where he was leading the department of family practice (prior to moving to Alabama). “You couldn’t ask too many questions,” she said. “And he never talked down to us, he wasn’t condescending. There were not a lot of doctors like that.”
Dr. Stephens spoke and wrote often about the importance of listening –about how it was vital to the “durable clinical relationship.” It was also vital to his writing and to his impact on the teachers of family medicine, said Dan Ostergaard, MD, who served as a residency director and in various staff leadership positions at the American Academy of Family Physicians, including in its division of education.
“He created a lot of aha moments for me, about where we came from and what we really need to be [as a specialty] and where we need to go,” said Dr. Ostergaard. “To be such a great thinker and a great writer, you have to be a great listener.”
“I can just visualize him,” he said, “leaning back in his chair while we were talking about residency criteria [or other issues], with a half-smile on his face and his reading glasses down his note, smoking his pipe and just looking at all of us, listening.”
Dr. Stephens’ papers are housed in the Center for the History of Family Medicine, a project of the AAFP Foundation.
Common MS treatment wears off more quickly in Black patients
new research suggests. In a study of almost 200 patients, Black participants with MS or NMOSD showed significantly more rapid B-cell repopulation 6-12 months after receiving anti-CD20 infusion therapy with rituximab or ocrelizumab (Rituxan, Ocrevus, Genentech) than did White participants.
“The results showed that this B-cell targeted therapy wore off more quickly in African Americans,” said study coinvestigator Gregg J. Silverman, MD, a professor at New York University.
He said that, although the study was more observational in design, “over time when people come back to the clinic, it gives you an idea of whether the agent is still working in their bodies.”
Overall, “our findings raise the question of whether the same therapy dose may be equally effective for all people,” coinvestigator Ilya Kister, MD, also from NYU, added in a press release.
Dr. Kister noted that this could have implications for the way Black patients with autoimmune diseases are treated in the future.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
More severe disease in Black patients
Anti-CD20 infusion therapy, or B-cell depletion therapy, is commonly used to treat autoimmune diseases, including MS and NMOSD. “While previous research has shown that this type of infusion therapy is effective for people with these diseases, we also know that Black people tend to have more severe courses of MS,” Dr. Kister said.
“We wanted to compare how quickly the B cells came back in Black people and White people after treatment,” he added.
Dr. Silverman noted that he has been “studying this agent in autoimmune disease for many years. And from all the different studies, I don’t think we had the right population to ask this question. Demographics were just reviewed as they were.”
The current study included 168 participants (mean age, 44 years; 71% women) who had a diagnosis of MS (n = 134) or NMOSD (n = 32) or who were considered to have MS or NMOSD (n = 2). In addition, 36% of the participants self-identified as Black or African American, 36% self-identified as White, and 28% self-identified as another race.
Flow cytometry results were available for all patients after undergoing anti-CD20 infusions at the NYU MS Care Center. Cluster analyses were conducted on the following B-cell subsets: CD19, CD20, IgD, and CD27. “B-cell repopulation was defined as any detectable number of CD19+ cells on flow cytometry,” the investigators reported.
Clinical implications?
Results showed that 29.8% of the full study group showed B-cell repopulation a mean of 6.8 months after infusion. In those with B-cell repopulation, 80.3% had IgD+/CD27– subsets, 11.6% had IgD–/CD27+, 6.2% had IgD–/CD27–, and 1.8% had IgD+/CD27+. These B-cell subset ratios did not differ significantly between the Black and White participants.
Interestingly, no patients showed B-cell repopulation before 4 months after infusion. From 4 to 6 months after infusion, there were no significant differences between the Black and White participants in terms of frequency of B-cell repopulation (20.8% vs. 17.9%, respectively; P = .79).
However, repopulation was significantly more frequent in the Black patients 6-12 months after infusion (76.2% vs. 33.3%; P = .02).
Overall, the findings “may have implications for clinical management of MS/NMOSD” in Black individuals, the investigators wrote.
“I was impressed by the differences we saw in responses of patients that were self-declaring as African Americans versus those who were Whites,” Dr. Silverman said. However, “as we say in science: it gives us an answer but it raises even more questions, which may well be important for helping us understand how the agent works and how the disease affects different people.”
Still, Dr. Silverman noted that the findings give clinicians using the agent “a signal that they should be very vigilant. It was an observation at one center, but we’re asking our colleagues [at other clinics] to think about being more careful as they review data with their patients.”
He added that future multicenter studies will allow these issues to be assessed more comprehensively. “This was a discovery study; it now needs validation; and maybe the next step would be looking into the mechanism.”
Dr. Silverman pointed out that the Food and Drug Administration–approved label for this type of therapy “allows for somewhat more frequent dosing. So that might be indicated if it’s found that it’s wearing off in an individual. Perhaps they should be treated more frequently?”
“At a minimum, this has raised our vigilance – and we’re interested to see what the feedback will be at the [AAN] meeting,” he added.
Real-world data
Commenting on the findings, Eric Klawiter, MD, associate professor of neurology at Harvard Medical School and director of the Multiple Sclerosis and NMO unit at Massachusetts General Hospital, both in Boston, noted that an important study factor was the focus on repopulation to identify specific groups “who may be early repopulators” as it relates to disease activity and disability progression in MS.
“I thought this was a nicely designed study that made good use of real-world data in MS and NMOSD,” added Dr. Klawiter, who was not involved with the research. He pointed out that timing was another interesting aspect of the study. “As we typically use these cell-depleting agents on an ‘every-6-month’ basis, the most pertinent time frame surrounds those that repopulate prior to 6 months.”
If the current study would have shown differences between the Black and White participants at that time point, “I think that would have been most pertinent from a clinical standpoint and a greater opportunity for intervention,” Dr. Klawiter said. “But we saw that, before 4 and 6 months, [the difference] wasn’t significant.”
Still, “after 6 months, the study demonstrates that Black people with MS and NMOSD may repopulate faster,” he added.
“The only real change a clinician could make would be to modify the frequency of the dosing. So if we can identify certain characteristics that would lead you to want to evaluate for the need of redosing sooner, I think that would be useful,” he said.
Specific characteristics identified in previous research include body mass index. “If there are also ethnicity factors, that would be an additional demographic factor that a clinician should pay close attention to,” said Dr. Klawiter.
He noted that his current practice is to check flow cytometry and B-cell counts at the time of a patient’s next infusion. “And if I’m seeing that B-cell levels are repleting at that time point, I am already then making adjustments with their next infusion as to the dosing frequency,” he added.
“This [study] may elucidate some of the potential reasons why we see some people replete their B cells faster than others, but I think additional studies are necessary to make that determination,” Dr. Klawiter concluded.
Genentech provided funding for the study. Dr. Silverman reported no relevant financial relationships. Dr. Klawiter reported having received research funds and consulting fees from Genentech.
A version of this article first appeared on Medscape.com.
new research suggests. In a study of almost 200 patients, Black participants with MS or NMOSD showed significantly more rapid B-cell repopulation 6-12 months after receiving anti-CD20 infusion therapy with rituximab or ocrelizumab (Rituxan, Ocrevus, Genentech) than did White participants.
“The results showed that this B-cell targeted therapy wore off more quickly in African Americans,” said study coinvestigator Gregg J. Silverman, MD, a professor at New York University.
He said that, although the study was more observational in design, “over time when people come back to the clinic, it gives you an idea of whether the agent is still working in their bodies.”
Overall, “our findings raise the question of whether the same therapy dose may be equally effective for all people,” coinvestigator Ilya Kister, MD, also from NYU, added in a press release.
Dr. Kister noted that this could have implications for the way Black patients with autoimmune diseases are treated in the future.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
More severe disease in Black patients
Anti-CD20 infusion therapy, or B-cell depletion therapy, is commonly used to treat autoimmune diseases, including MS and NMOSD. “While previous research has shown that this type of infusion therapy is effective for people with these diseases, we also know that Black people tend to have more severe courses of MS,” Dr. Kister said.
“We wanted to compare how quickly the B cells came back in Black people and White people after treatment,” he added.
Dr. Silverman noted that he has been “studying this agent in autoimmune disease for many years. And from all the different studies, I don’t think we had the right population to ask this question. Demographics were just reviewed as they were.”
The current study included 168 participants (mean age, 44 years; 71% women) who had a diagnosis of MS (n = 134) or NMOSD (n = 32) or who were considered to have MS or NMOSD (n = 2). In addition, 36% of the participants self-identified as Black or African American, 36% self-identified as White, and 28% self-identified as another race.
Flow cytometry results were available for all patients after undergoing anti-CD20 infusions at the NYU MS Care Center. Cluster analyses were conducted on the following B-cell subsets: CD19, CD20, IgD, and CD27. “B-cell repopulation was defined as any detectable number of CD19+ cells on flow cytometry,” the investigators reported.
Clinical implications?
Results showed that 29.8% of the full study group showed B-cell repopulation a mean of 6.8 months after infusion. In those with B-cell repopulation, 80.3% had IgD+/CD27– subsets, 11.6% had IgD–/CD27+, 6.2% had IgD–/CD27–, and 1.8% had IgD+/CD27+. These B-cell subset ratios did not differ significantly between the Black and White participants.
Interestingly, no patients showed B-cell repopulation before 4 months after infusion. From 4 to 6 months after infusion, there were no significant differences between the Black and White participants in terms of frequency of B-cell repopulation (20.8% vs. 17.9%, respectively; P = .79).
However, repopulation was significantly more frequent in the Black patients 6-12 months after infusion (76.2% vs. 33.3%; P = .02).
Overall, the findings “may have implications for clinical management of MS/NMOSD” in Black individuals, the investigators wrote.
“I was impressed by the differences we saw in responses of patients that were self-declaring as African Americans versus those who were Whites,” Dr. Silverman said. However, “as we say in science: it gives us an answer but it raises even more questions, which may well be important for helping us understand how the agent works and how the disease affects different people.”
Still, Dr. Silverman noted that the findings give clinicians using the agent “a signal that they should be very vigilant. It was an observation at one center, but we’re asking our colleagues [at other clinics] to think about being more careful as they review data with their patients.”
He added that future multicenter studies will allow these issues to be assessed more comprehensively. “This was a discovery study; it now needs validation; and maybe the next step would be looking into the mechanism.”
Dr. Silverman pointed out that the Food and Drug Administration–approved label for this type of therapy “allows for somewhat more frequent dosing. So that might be indicated if it’s found that it’s wearing off in an individual. Perhaps they should be treated more frequently?”
“At a minimum, this has raised our vigilance – and we’re interested to see what the feedback will be at the [AAN] meeting,” he added.
Real-world data
Commenting on the findings, Eric Klawiter, MD, associate professor of neurology at Harvard Medical School and director of the Multiple Sclerosis and NMO unit at Massachusetts General Hospital, both in Boston, noted that an important study factor was the focus on repopulation to identify specific groups “who may be early repopulators” as it relates to disease activity and disability progression in MS.
“I thought this was a nicely designed study that made good use of real-world data in MS and NMOSD,” added Dr. Klawiter, who was not involved with the research. He pointed out that timing was another interesting aspect of the study. “As we typically use these cell-depleting agents on an ‘every-6-month’ basis, the most pertinent time frame surrounds those that repopulate prior to 6 months.”
If the current study would have shown differences between the Black and White participants at that time point, “I think that would have been most pertinent from a clinical standpoint and a greater opportunity for intervention,” Dr. Klawiter said. “But we saw that, before 4 and 6 months, [the difference] wasn’t significant.”
Still, “after 6 months, the study demonstrates that Black people with MS and NMOSD may repopulate faster,” he added.
“The only real change a clinician could make would be to modify the frequency of the dosing. So if we can identify certain characteristics that would lead you to want to evaluate for the need of redosing sooner, I think that would be useful,” he said.
Specific characteristics identified in previous research include body mass index. “If there are also ethnicity factors, that would be an additional demographic factor that a clinician should pay close attention to,” said Dr. Klawiter.
He noted that his current practice is to check flow cytometry and B-cell counts at the time of a patient’s next infusion. “And if I’m seeing that B-cell levels are repleting at that time point, I am already then making adjustments with their next infusion as to the dosing frequency,” he added.
“This [study] may elucidate some of the potential reasons why we see some people replete their B cells faster than others, but I think additional studies are necessary to make that determination,” Dr. Klawiter concluded.
Genentech provided funding for the study. Dr. Silverman reported no relevant financial relationships. Dr. Klawiter reported having received research funds and consulting fees from Genentech.
A version of this article first appeared on Medscape.com.
new research suggests. In a study of almost 200 patients, Black participants with MS or NMOSD showed significantly more rapid B-cell repopulation 6-12 months after receiving anti-CD20 infusion therapy with rituximab or ocrelizumab (Rituxan, Ocrevus, Genentech) than did White participants.
“The results showed that this B-cell targeted therapy wore off more quickly in African Americans,” said study coinvestigator Gregg J. Silverman, MD, a professor at New York University.
He said that, although the study was more observational in design, “over time when people come back to the clinic, it gives you an idea of whether the agent is still working in their bodies.”
Overall, “our findings raise the question of whether the same therapy dose may be equally effective for all people,” coinvestigator Ilya Kister, MD, also from NYU, added in a press release.
Dr. Kister noted that this could have implications for the way Black patients with autoimmune diseases are treated in the future.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
More severe disease in Black patients
Anti-CD20 infusion therapy, or B-cell depletion therapy, is commonly used to treat autoimmune diseases, including MS and NMOSD. “While previous research has shown that this type of infusion therapy is effective for people with these diseases, we also know that Black people tend to have more severe courses of MS,” Dr. Kister said.
“We wanted to compare how quickly the B cells came back in Black people and White people after treatment,” he added.
Dr. Silverman noted that he has been “studying this agent in autoimmune disease for many years. And from all the different studies, I don’t think we had the right population to ask this question. Demographics were just reviewed as they were.”
The current study included 168 participants (mean age, 44 years; 71% women) who had a diagnosis of MS (n = 134) or NMOSD (n = 32) or who were considered to have MS or NMOSD (n = 2). In addition, 36% of the participants self-identified as Black or African American, 36% self-identified as White, and 28% self-identified as another race.
Flow cytometry results were available for all patients after undergoing anti-CD20 infusions at the NYU MS Care Center. Cluster analyses were conducted on the following B-cell subsets: CD19, CD20, IgD, and CD27. “B-cell repopulation was defined as any detectable number of CD19+ cells on flow cytometry,” the investigators reported.
Clinical implications?
Results showed that 29.8% of the full study group showed B-cell repopulation a mean of 6.8 months after infusion. In those with B-cell repopulation, 80.3% had IgD+/CD27– subsets, 11.6% had IgD–/CD27+, 6.2% had IgD–/CD27–, and 1.8% had IgD+/CD27+. These B-cell subset ratios did not differ significantly between the Black and White participants.
Interestingly, no patients showed B-cell repopulation before 4 months after infusion. From 4 to 6 months after infusion, there were no significant differences between the Black and White participants in terms of frequency of B-cell repopulation (20.8% vs. 17.9%, respectively; P = .79).
However, repopulation was significantly more frequent in the Black patients 6-12 months after infusion (76.2% vs. 33.3%; P = .02).
Overall, the findings “may have implications for clinical management of MS/NMOSD” in Black individuals, the investigators wrote.
“I was impressed by the differences we saw in responses of patients that were self-declaring as African Americans versus those who were Whites,” Dr. Silverman said. However, “as we say in science: it gives us an answer but it raises even more questions, which may well be important for helping us understand how the agent works and how the disease affects different people.”
Still, Dr. Silverman noted that the findings give clinicians using the agent “a signal that they should be very vigilant. It was an observation at one center, but we’re asking our colleagues [at other clinics] to think about being more careful as they review data with their patients.”
He added that future multicenter studies will allow these issues to be assessed more comprehensively. “This was a discovery study; it now needs validation; and maybe the next step would be looking into the mechanism.”
Dr. Silverman pointed out that the Food and Drug Administration–approved label for this type of therapy “allows for somewhat more frequent dosing. So that might be indicated if it’s found that it’s wearing off in an individual. Perhaps they should be treated more frequently?”
“At a minimum, this has raised our vigilance – and we’re interested to see what the feedback will be at the [AAN] meeting,” he added.
Real-world data
Commenting on the findings, Eric Klawiter, MD, associate professor of neurology at Harvard Medical School and director of the Multiple Sclerosis and NMO unit at Massachusetts General Hospital, both in Boston, noted that an important study factor was the focus on repopulation to identify specific groups “who may be early repopulators” as it relates to disease activity and disability progression in MS.
“I thought this was a nicely designed study that made good use of real-world data in MS and NMOSD,” added Dr. Klawiter, who was not involved with the research. He pointed out that timing was another interesting aspect of the study. “As we typically use these cell-depleting agents on an ‘every-6-month’ basis, the most pertinent time frame surrounds those that repopulate prior to 6 months.”
If the current study would have shown differences between the Black and White participants at that time point, “I think that would have been most pertinent from a clinical standpoint and a greater opportunity for intervention,” Dr. Klawiter said. “But we saw that, before 4 and 6 months, [the difference] wasn’t significant.”
Still, “after 6 months, the study demonstrates that Black people with MS and NMOSD may repopulate faster,” he added.
“The only real change a clinician could make would be to modify the frequency of the dosing. So if we can identify certain characteristics that would lead you to want to evaluate for the need of redosing sooner, I think that would be useful,” he said.
Specific characteristics identified in previous research include body mass index. “If there are also ethnicity factors, that would be an additional demographic factor that a clinician should pay close attention to,” said Dr. Klawiter.
He noted that his current practice is to check flow cytometry and B-cell counts at the time of a patient’s next infusion. “And if I’m seeing that B-cell levels are repleting at that time point, I am already then making adjustments with their next infusion as to the dosing frequency,” he added.
“This [study] may elucidate some of the potential reasons why we see some people replete their B cells faster than others, but I think additional studies are necessary to make that determination,” Dr. Klawiter concluded.
Genentech provided funding for the study. Dr. Silverman reported no relevant financial relationships. Dr. Klawiter reported having received research funds and consulting fees from Genentech.
A version of this article first appeared on Medscape.com.
FROM AAN 2021
Teen tanning bed ban would prevent more than 15,000 melanoma cases
and cost less than other, well-established public health interventions, according to a microsimulation of that age group’s virtual life course.
“Even with extensive sensitivity analyses on the costs of inspections, noncompliance with a ban, and the risk of developing melanoma in those who have used tanning beds, a ban can be considered highly cost effective,” Antoine Eskander, MD, ScM, of the University of Toronto, and associates said in Cancer.
Compared with no ban, such an intervention could save over $205 million in lifetime health care costs among the 17.1 million young people (based on the 2010 Census population) who would be affected, they said.
The more than 15,000 melanoma cases and 3,300 recurrences prevented would save $12 per average minor after adjusting for societal costs, such as lost productivity, formal and informal health care, economic losses to the tanning bed industry, and the need for monitoring, the investigators reported.
Switching to quality-adjusted life-years shows an improvement of 0.0002 QALYs per child for a ban, based on an overall cost of almost $24.9 per QALY, compared with no ban, they said, which makes it “more cost effective than many well-established public health interventions”:
- Processed meats taxation ($270/QALY).
- Smoking education campaign ($1,337/QALY).
- Cervical cancer screening ($2,166/QALY).
- Breast cancer screening ($29,284/QALY).
- Lung cancer screening ($49,200-$96,700/QALY).
Among the many parameters included in the microsimulation were the odds ratio of developing melanoma from exposure to tanning beds before age 25 (1.35), melanoma stage at presentation, risk of recurrence, and the cost of four annual inspections for each of the nation’s more than 13,000 tanning salons, Dr. Eskander and associates explained.
and cost less than other, well-established public health interventions, according to a microsimulation of that age group’s virtual life course.
“Even with extensive sensitivity analyses on the costs of inspections, noncompliance with a ban, and the risk of developing melanoma in those who have used tanning beds, a ban can be considered highly cost effective,” Antoine Eskander, MD, ScM, of the University of Toronto, and associates said in Cancer.
Compared with no ban, such an intervention could save over $205 million in lifetime health care costs among the 17.1 million young people (based on the 2010 Census population) who would be affected, they said.
The more than 15,000 melanoma cases and 3,300 recurrences prevented would save $12 per average minor after adjusting for societal costs, such as lost productivity, formal and informal health care, economic losses to the tanning bed industry, and the need for monitoring, the investigators reported.
Switching to quality-adjusted life-years shows an improvement of 0.0002 QALYs per child for a ban, based on an overall cost of almost $24.9 per QALY, compared with no ban, they said, which makes it “more cost effective than many well-established public health interventions”:
- Processed meats taxation ($270/QALY).
- Smoking education campaign ($1,337/QALY).
- Cervical cancer screening ($2,166/QALY).
- Breast cancer screening ($29,284/QALY).
- Lung cancer screening ($49,200-$96,700/QALY).
Among the many parameters included in the microsimulation were the odds ratio of developing melanoma from exposure to tanning beds before age 25 (1.35), melanoma stage at presentation, risk of recurrence, and the cost of four annual inspections for each of the nation’s more than 13,000 tanning salons, Dr. Eskander and associates explained.
and cost less than other, well-established public health interventions, according to a microsimulation of that age group’s virtual life course.
“Even with extensive sensitivity analyses on the costs of inspections, noncompliance with a ban, and the risk of developing melanoma in those who have used tanning beds, a ban can be considered highly cost effective,” Antoine Eskander, MD, ScM, of the University of Toronto, and associates said in Cancer.
Compared with no ban, such an intervention could save over $205 million in lifetime health care costs among the 17.1 million young people (based on the 2010 Census population) who would be affected, they said.
The more than 15,000 melanoma cases and 3,300 recurrences prevented would save $12 per average minor after adjusting for societal costs, such as lost productivity, formal and informal health care, economic losses to the tanning bed industry, and the need for monitoring, the investigators reported.
Switching to quality-adjusted life-years shows an improvement of 0.0002 QALYs per child for a ban, based on an overall cost of almost $24.9 per QALY, compared with no ban, they said, which makes it “more cost effective than many well-established public health interventions”:
- Processed meats taxation ($270/QALY).
- Smoking education campaign ($1,337/QALY).
- Cervical cancer screening ($2,166/QALY).
- Breast cancer screening ($29,284/QALY).
- Lung cancer screening ($49,200-$96,700/QALY).
Among the many parameters included in the microsimulation were the odds ratio of developing melanoma from exposure to tanning beds before age 25 (1.35), melanoma stage at presentation, risk of recurrence, and the cost of four annual inspections for each of the nation’s more than 13,000 tanning salons, Dr. Eskander and associates explained.
FROM CANCER
Cortical surface changes linked to sensorimotor abnormalities in schizophrenia
Schizophrenia patients with parkinsonism show unique neurodevelopmental signatures on imaging that involve the sensorimotor system, according to MRI data from 73 adult schizophrenia patients.
Although sensorimotor abnormalities are common in patients with schizophrenia, the neurobiology of parkinsonism in particular is not well understood. Aberrant neurodevelopment is considered a potential mechanism of action for the emergence of such abnormalities, wrote Robert Christian Wolf, MD, of Heidelberg (Germany) University, and colleagues.
In a multimodal MRI study published in Schizophrenia Research, the investigators identified 38 adults with schizophrenia and parkinsonism (SZ-P), 35 schizophrenia patients without parkinsonism (SZ-nonP), and 20 healthy controls.
Parkinsonism was defined as scores of 4 or higher on the Simpson-Angus Scale, while non-Parkinsonism schizophrenia patients had scores of 1 or less.
The researchers examined cortical and subcortical gray-matter volume, as well as three cortical surface markers related to neurodevelopment: cortical thickness (CTh), complexity of cortical folding (CCF), and sulcus depth.
Overall, the SZ-P patients showed increased CCF in the left supplementary motor cortex (SMC) and decreased left postcentral sulcus depth, compared with SZ-nonP patients (P < .05). The left SMC also showed increased CCF, compared with healthy controls – but that difference was not significant.
Both SZ-P and SZ-nonP patients showed higher levels of activity in the left SMC, compared with controls, and activity was higher in SZ-nonP patients, compared with SZ-P patients. In addition, Dr. Wolf and colleagues reported.
“Overall, the data support the notion that cortical features of distinct neurodevelopmental origin, particularly cortical folding indices such as CCF and sulcus depth, contribute to the pathogenesis of parkinsonism in SZ,” the researchers said.
The study findings were limited by several factors, including the cross-sectional design, the challenges of using the potential restraint inherent in the Simpson-Angus Scale to diagnose parkinsonism, the inability to gauge the impact of lifetime exposure to antipsychotics, and the inability to identify changes in brain stem nuclei, the researchers noted. However, the results suggest the impact of cortical development on parkinsonism in schizophrenia,.
“Cortical surface changes in the sensorimotor system suggest abnormal neurodevelopmental processes that are associated with increased risk for intrinsic sensorimotor abnormalities in SZ and related psychotic disorders,” they concluded.
The study was supported by the German Research Foundation and the German Federal Ministry of Education and Research. The researchers disclosed no financial conflicts.
Schizophrenia patients with parkinsonism show unique neurodevelopmental signatures on imaging that involve the sensorimotor system, according to MRI data from 73 adult schizophrenia patients.
Although sensorimotor abnormalities are common in patients with schizophrenia, the neurobiology of parkinsonism in particular is not well understood. Aberrant neurodevelopment is considered a potential mechanism of action for the emergence of such abnormalities, wrote Robert Christian Wolf, MD, of Heidelberg (Germany) University, and colleagues.
In a multimodal MRI study published in Schizophrenia Research, the investigators identified 38 adults with schizophrenia and parkinsonism (SZ-P), 35 schizophrenia patients without parkinsonism (SZ-nonP), and 20 healthy controls.
Parkinsonism was defined as scores of 4 or higher on the Simpson-Angus Scale, while non-Parkinsonism schizophrenia patients had scores of 1 or less.
The researchers examined cortical and subcortical gray-matter volume, as well as three cortical surface markers related to neurodevelopment: cortical thickness (CTh), complexity of cortical folding (CCF), and sulcus depth.
Overall, the SZ-P patients showed increased CCF in the left supplementary motor cortex (SMC) and decreased left postcentral sulcus depth, compared with SZ-nonP patients (P < .05). The left SMC also showed increased CCF, compared with healthy controls – but that difference was not significant.
Both SZ-P and SZ-nonP patients showed higher levels of activity in the left SMC, compared with controls, and activity was higher in SZ-nonP patients, compared with SZ-P patients. In addition, Dr. Wolf and colleagues reported.
“Overall, the data support the notion that cortical features of distinct neurodevelopmental origin, particularly cortical folding indices such as CCF and sulcus depth, contribute to the pathogenesis of parkinsonism in SZ,” the researchers said.
The study findings were limited by several factors, including the cross-sectional design, the challenges of using the potential restraint inherent in the Simpson-Angus Scale to diagnose parkinsonism, the inability to gauge the impact of lifetime exposure to antipsychotics, and the inability to identify changes in brain stem nuclei, the researchers noted. However, the results suggest the impact of cortical development on parkinsonism in schizophrenia,.
“Cortical surface changes in the sensorimotor system suggest abnormal neurodevelopmental processes that are associated with increased risk for intrinsic sensorimotor abnormalities in SZ and related psychotic disorders,” they concluded.
The study was supported by the German Research Foundation and the German Federal Ministry of Education and Research. The researchers disclosed no financial conflicts.
Schizophrenia patients with parkinsonism show unique neurodevelopmental signatures on imaging that involve the sensorimotor system, according to MRI data from 73 adult schizophrenia patients.
Although sensorimotor abnormalities are common in patients with schizophrenia, the neurobiology of parkinsonism in particular is not well understood. Aberrant neurodevelopment is considered a potential mechanism of action for the emergence of such abnormalities, wrote Robert Christian Wolf, MD, of Heidelberg (Germany) University, and colleagues.
In a multimodal MRI study published in Schizophrenia Research, the investigators identified 38 adults with schizophrenia and parkinsonism (SZ-P), 35 schizophrenia patients without parkinsonism (SZ-nonP), and 20 healthy controls.
Parkinsonism was defined as scores of 4 or higher on the Simpson-Angus Scale, while non-Parkinsonism schizophrenia patients had scores of 1 or less.
The researchers examined cortical and subcortical gray-matter volume, as well as three cortical surface markers related to neurodevelopment: cortical thickness (CTh), complexity of cortical folding (CCF), and sulcus depth.
Overall, the SZ-P patients showed increased CCF in the left supplementary motor cortex (SMC) and decreased left postcentral sulcus depth, compared with SZ-nonP patients (P < .05). The left SMC also showed increased CCF, compared with healthy controls – but that difference was not significant.
Both SZ-P and SZ-nonP patients showed higher levels of activity in the left SMC, compared with controls, and activity was higher in SZ-nonP patients, compared with SZ-P patients. In addition, Dr. Wolf and colleagues reported.
“Overall, the data support the notion that cortical features of distinct neurodevelopmental origin, particularly cortical folding indices such as CCF and sulcus depth, contribute to the pathogenesis of parkinsonism in SZ,” the researchers said.
The study findings were limited by several factors, including the cross-sectional design, the challenges of using the potential restraint inherent in the Simpson-Angus Scale to diagnose parkinsonism, the inability to gauge the impact of lifetime exposure to antipsychotics, and the inability to identify changes in brain stem nuclei, the researchers noted. However, the results suggest the impact of cortical development on parkinsonism in schizophrenia,.
“Cortical surface changes in the sensorimotor system suggest abnormal neurodevelopmental processes that are associated with increased risk for intrinsic sensorimotor abnormalities in SZ and related psychotic disorders,” they concluded.
The study was supported by the German Research Foundation and the German Federal Ministry of Education and Research. The researchers disclosed no financial conflicts.
FROM SCHIZOPHRENIA RESEARCH