Kate Johnson

Older age and higher ferritin levels at hospital admission predict severe illness in COVID-related multisystem inflammatory syndrome in children (MIS-C), according to a Canadian multicenter cohort study.

The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.

“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”

The data were published  in the Canadian Medical Association Journal.
 

A multinational study

The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.

Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
 

Older age as a risk

The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.

The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
 

Features of MIS-C

Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson. 

The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”

Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”  
 

‘Differences across countries’

Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.

Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.

“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.

What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”

This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.

A version of this article first appeared on Medscape.com.

Older age and higher ferritin levels at hospital admission predict severe illness in COVID-related multisystem inflammatory syndrome in children (MIS-C), according to a Canadian multicenter cohort study.

The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.

“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”

The data were published  in the Canadian Medical Association Journal.
 

A multinational study

The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.

Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
 

Older age as a risk

The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.

The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
 

Features of MIS-C

Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson. 

The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”

Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”  
 

‘Differences across countries’

Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.

Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.

“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.

What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”

This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.

A version of this article first appeared on Medscape.com.

Older age and higher ferritin levels at hospital admission predict severe illness in COVID-related multisystem inflammatory syndrome in children (MIS-C), according to a Canadian multicenter cohort study.

The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.

“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”

The data were published  in the Canadian Medical Association Journal.
 

A multinational study

The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.

Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
 

Older age as a risk

The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.

The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
 

Features of MIS-C

Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson. 

The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”

Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”  
 

‘Differences across countries’

Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.

Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.

“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.

What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”

This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.

A version of this article first appeared on Medscape.com.

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

Cancer care is not a top priority for the United Nations agency that is helping Ukrainian refugees across the border into neighboring countries, which makes the role of oncology groups vitally important.

“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.

“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”

Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.

He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.

With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.

“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”

So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.

“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”

“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.

Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.

Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”

Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.

Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”

Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”

The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.

“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.

In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.

“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”

Separately, there is also an ASCO resource page, as well as an ECO resource page.

The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.

Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”

A version of this article first appeared on Medscape.com.

Cancer care is not a top priority for the United Nations agency that is helping Ukrainian refugees across the border into neighboring countries, which makes the role of oncology groups vitally important.

“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.

“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”

Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.

He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.

With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.

“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”

So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.

“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”

“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.

Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.

Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”

Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.

Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”

Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”

The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.

“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.

In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.

“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”

Separately, there is also an ASCO resource page, as well as an ECO resource page.

The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.

Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”

A version of this article first appeared on Medscape.com.

Cancer care is not a top priority for the United Nations agency that is helping Ukrainian refugees across the border into neighboring countries, which makes the role of oncology groups vitally important.

“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.

“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”

Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.

He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.

With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.

“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”

So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.

“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”

“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.

Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.

Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”

Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.

Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”

Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”

The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.

“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.

In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.

“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”

Separately, there is also an ASCO resource page, as well as an ECO resource page.

The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.

Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”

A version of this article first appeared on Medscape.com.

The pediatric oncology unit in Kyiv’s National Cancer Institute is empty, with all the children evacuated to safer hospitals in Western Ukraine or further, making it a good place to talk on Zoom.

Against a backdrop of colorful animals painted on the wall, Oleksandr Stakhovskyi, MD, PhD, speaks optimistically about the future of his city, his country, and even his patients, despite acknowledging that his surgical hands are now trained to use a machine gun.

“It’s not as bad as last week,” he laughs, explaining that residents of Kyiv are more relaxed now, despite the air raid sirens, because the city’s anti-missile system has thus far kept them safe.

Even still, missiles have continued hitting civilian residences and Dr. Stakhovskyi, a urologic-oncology surgeon, has evacuated his wife and children out of the country, as have 70% of his colleagues. But for those who stayed in Kyiv, there is a strong resolve.

“People working in IT, in law, in other professions — they just took the guns and stayed in Kyiv,” he said in an interview. “They are just civilians, armed, trying to protect and fortify Kyiv — to make it unbreakable.”

Dr. Stakhovskyi doesn’t have a background in the military, but he now knows how to use a machine gun. “I am a super-specialized oncologist, [but] I realize if I leave right now it will give the Russians momentum to come in. The longer it takes, the weaker the opponent army will become, and we are more and more optimistic,” he said.

In Kyiv, Dr. Stakhovskyi is working half the time at the cancer hospital and the other half at the nearby military hospital, but he said so far war casualties are minimal within the city, and even the flow of patients with cancer has reduced.

“I had my surgeries planned up until the end of March, but when the war started, they were all postponed,” he said. Emergency cancer surgeries have continued, and now there is talk of resuming some others. “We will stratify patients into categories based on need,” he said. “For those patients whose surgery can basically stop the disease and they don’t need neoadjuvant chemo, we’ll probably be doing those.”

Medical oncology clinics have also resumed, said Dr. Stakhovskyi, but the volume of patients is low, because many have left the city. An estimated 3.3 million people have left Ukraine since the Russian invasion on February 24.

Across the country, in Lviv near the Polish border, another surgical oncologist tells a different story. Andriy Hrynkiv, MD, from Lviv Regional Cancer Center, says his hospital has seen a dramatic increase in patients, displaced internally from areas where the medical infrastructure has collapsed.

“Russian forces have destroyed more than 117 hospitals, 43 ambulances have been shot at, 6 doctors have been killed, and 13 wounded,” Dr. Hrynkiv said. In the city of Mariupol, “doctors and patients have been taken hostage,” he said, used by Russian forces as a human shield. In Kharkiv, with approximately 1.5 million residents, the only oncologic hospital has been destroyed.

There is a shortage and instability of medical supplies including all iodine-containing medications that citizens are stocking up on in the face of a potential nuclear attack, he said.

Dr. Hrynkiv was speaking on a webcast organized by the American Society of Clinical Oncology (ASCO) and European Cancer Organisation (ECO).

The two organizations are collaborating with each other and the World Health Organization to create a special network that is aiming to connect professionals, academic and clinical centers, and patient groups.

Additionally, the Ukranian Society of Clinical Oncology (USCO), cofounded by Dr. Stakhovskyi, is trying to keep patients connected with nongovernment organizations.

“These patient organizations moved west when the war started, but they still use us to help them make contact with foreign doctors,” he said. “We have tried to centralize this process but it’s very difficult because patients and organizations are also calling doctors and centers directly looking for treatment options.”

He says USCO is also coordinating the distribution of a donation of immunotherapy pembrolizumab (Keytruda) from pharmaceutical company Merck Sharp & Dohme. “It’s a huge influx of this drug,” he says. “They’ve promised something like 2,000 doses to cover 230 patients for 3 months at least. Usually this is not an easy drug to access for people in Ukraine because it’s really expensive.”

Dr. Stakhovskyi said the optimism he feels is fueled by the support that Ukrainians feel from the rest of the world.

“We see the reaction of our international colleagues. It is so impressive and touching — lots of my ex-professors are texting me and sending me messages from all over the place, from Germany, from Canada, from France, from the United States,” he said. “And if we can be optimistic for ourselves, definitely that translates to our patients.”

A version of this article first appeared on Medscape.com.

The pediatric oncology unit in Kyiv’s National Cancer Institute is empty, with all the children evacuated to safer hospitals in Western Ukraine or further, making it a good place to talk on Zoom.

Against a backdrop of colorful animals painted on the wall, Oleksandr Stakhovskyi, MD, PhD, speaks optimistically about the future of his city, his country, and even his patients, despite acknowledging that his surgical hands are now trained to use a machine gun.

“It’s not as bad as last week,” he laughs, explaining that residents of Kyiv are more relaxed now, despite the air raid sirens, because the city’s anti-missile system has thus far kept them safe.

Even still, missiles have continued hitting civilian residences and Dr. Stakhovskyi, a urologic-oncology surgeon, has evacuated his wife and children out of the country, as have 70% of his colleagues. But for those who stayed in Kyiv, there is a strong resolve.

“People working in IT, in law, in other professions — they just took the guns and stayed in Kyiv,” he said in an interview. “They are just civilians, armed, trying to protect and fortify Kyiv — to make it unbreakable.”

Dr. Stakhovskyi doesn’t have a background in the military, but he now knows how to use a machine gun. “I am a super-specialized oncologist, [but] I realize if I leave right now it will give the Russians momentum to come in. The longer it takes, the weaker the opponent army will become, and we are more and more optimistic,” he said.

In Kyiv, Dr. Stakhovskyi is working half the time at the cancer hospital and the other half at the nearby military hospital, but he said so far war casualties are minimal within the city, and even the flow of patients with cancer has reduced.

“I had my surgeries planned up until the end of March, but when the war started, they were all postponed,” he said. Emergency cancer surgeries have continued, and now there is talk of resuming some others. “We will stratify patients into categories based on need,” he said. “For those patients whose surgery can basically stop the disease and they don’t need neoadjuvant chemo, we’ll probably be doing those.”

Medical oncology clinics have also resumed, said Dr. Stakhovskyi, but the volume of patients is low, because many have left the city. An estimated 3.3 million people have left Ukraine since the Russian invasion on February 24.

Across the country, in Lviv near the Polish border, another surgical oncologist tells a different story. Andriy Hrynkiv, MD, from Lviv Regional Cancer Center, says his hospital has seen a dramatic increase in patients, displaced internally from areas where the medical infrastructure has collapsed.

“Russian forces have destroyed more than 117 hospitals, 43 ambulances have been shot at, 6 doctors have been killed, and 13 wounded,” Dr. Hrynkiv said. In the city of Mariupol, “doctors and patients have been taken hostage,” he said, used by Russian forces as a human shield. In Kharkiv, with approximately 1.5 million residents, the only oncologic hospital has been destroyed.

There is a shortage and instability of medical supplies including all iodine-containing medications that citizens are stocking up on in the face of a potential nuclear attack, he said.

Dr. Hrynkiv was speaking on a webcast organized by the American Society of Clinical Oncology (ASCO) and European Cancer Organisation (ECO).

The two organizations are collaborating with each other and the World Health Organization to create a special network that is aiming to connect professionals, academic and clinical centers, and patient groups.

Additionally, the Ukranian Society of Clinical Oncology (USCO), cofounded by Dr. Stakhovskyi, is trying to keep patients connected with nongovernment organizations.

“These patient organizations moved west when the war started, but they still use us to help them make contact with foreign doctors,” he said. “We have tried to centralize this process but it’s very difficult because patients and organizations are also calling doctors and centers directly looking for treatment options.”

He says USCO is also coordinating the distribution of a donation of immunotherapy pembrolizumab (Keytruda) from pharmaceutical company Merck Sharp & Dohme. “It’s a huge influx of this drug,” he says. “They’ve promised something like 2,000 doses to cover 230 patients for 3 months at least. Usually this is not an easy drug to access for people in Ukraine because it’s really expensive.”

Dr. Stakhovskyi said the optimism he feels is fueled by the support that Ukrainians feel from the rest of the world.

“We see the reaction of our international colleagues. It is so impressive and touching — lots of my ex-professors are texting me and sending me messages from all over the place, from Germany, from Canada, from France, from the United States,” he said. “And if we can be optimistic for ourselves, definitely that translates to our patients.”

A version of this article first appeared on Medscape.com.

The pediatric oncology unit in Kyiv’s National Cancer Institute is empty, with all the children evacuated to safer hospitals in Western Ukraine or further, making it a good place to talk on Zoom.

Against a backdrop of colorful animals painted on the wall, Oleksandr Stakhovskyi, MD, PhD, speaks optimistically about the future of his city, his country, and even his patients, despite acknowledging that his surgical hands are now trained to use a machine gun.

“It’s not as bad as last week,” he laughs, explaining that residents of Kyiv are more relaxed now, despite the air raid sirens, because the city’s anti-missile system has thus far kept them safe.

Even still, missiles have continued hitting civilian residences and Dr. Stakhovskyi, a urologic-oncology surgeon, has evacuated his wife and children out of the country, as have 70% of his colleagues. But for those who stayed in Kyiv, there is a strong resolve.

“People working in IT, in law, in other professions — they just took the guns and stayed in Kyiv,” he said in an interview. “They are just civilians, armed, trying to protect and fortify Kyiv — to make it unbreakable.”

Dr. Stakhovskyi doesn’t have a background in the military, but he now knows how to use a machine gun. “I am a super-specialized oncologist, [but] I realize if I leave right now it will give the Russians momentum to come in. The longer it takes, the weaker the opponent army will become, and we are more and more optimistic,” he said.

In Kyiv, Dr. Stakhovskyi is working half the time at the cancer hospital and the other half at the nearby military hospital, but he said so far war casualties are minimal within the city, and even the flow of patients with cancer has reduced.

“I had my surgeries planned up until the end of March, but when the war started, they were all postponed,” he said. Emergency cancer surgeries have continued, and now there is talk of resuming some others. “We will stratify patients into categories based on need,” he said. “For those patients whose surgery can basically stop the disease and they don’t need neoadjuvant chemo, we’ll probably be doing those.”

Medical oncology clinics have also resumed, said Dr. Stakhovskyi, but the volume of patients is low, because many have left the city. An estimated 3.3 million people have left Ukraine since the Russian invasion on February 24.

Across the country, in Lviv near the Polish border, another surgical oncologist tells a different story. Andriy Hrynkiv, MD, from Lviv Regional Cancer Center, says his hospital has seen a dramatic increase in patients, displaced internally from areas where the medical infrastructure has collapsed.

“Russian forces have destroyed more than 117 hospitals, 43 ambulances have been shot at, 6 doctors have been killed, and 13 wounded,” Dr. Hrynkiv said. In the city of Mariupol, “doctors and patients have been taken hostage,” he said, used by Russian forces as a human shield. In Kharkiv, with approximately 1.5 million residents, the only oncologic hospital has been destroyed.

There is a shortage and instability of medical supplies including all iodine-containing medications that citizens are stocking up on in the face of a potential nuclear attack, he said.

Dr. Hrynkiv was speaking on a webcast organized by the American Society of Clinical Oncology (ASCO) and European Cancer Organisation (ECO).

The two organizations are collaborating with each other and the World Health Organization to create a special network that is aiming to connect professionals, academic and clinical centers, and patient groups.

Additionally, the Ukranian Society of Clinical Oncology (USCO), cofounded by Dr. Stakhovskyi, is trying to keep patients connected with nongovernment organizations.

“These patient organizations moved west when the war started, but they still use us to help them make contact with foreign doctors,” he said. “We have tried to centralize this process but it’s very difficult because patients and organizations are also calling doctors and centers directly looking for treatment options.”

He says USCO is also coordinating the distribution of a donation of immunotherapy pembrolizumab (Keytruda) from pharmaceutical company Merck Sharp & Dohme. “It’s a huge influx of this drug,” he says. “They’ve promised something like 2,000 doses to cover 230 patients for 3 months at least. Usually this is not an easy drug to access for people in Ukraine because it’s really expensive.”

Dr. Stakhovskyi said the optimism he feels is fueled by the support that Ukrainians feel from the rest of the world.

“We see the reaction of our international colleagues. It is so impressive and touching — lots of my ex-professors are texting me and sending me messages from all over the place, from Germany, from Canada, from France, from the United States,” he said. “And if we can be optimistic for ourselves, definitely that translates to our patients.”

A version of this article first appeared on Medscape.com.

For the past 2 years, oncology practitioners around the world have struggled with the same dilemma: how to maintain their patients’ cancer care without exposing them to COVID-19. Regardless of the country, language, or even which wave of the pandemic, the conversations have likely been very similar: weighing risks versuss benefits, and individualizing each patient’s pandemic cancer plan.

But one question most oncologists have probably overlooked in these discussions is about where their patients get their COVID information – or misinformation.

Surprisingly, this seemingly small detail could make a big difference in a patient’s prognosis.

A recent study found that adult cancer patients are more vulnerable to COVID misinformation, compared with healthy controls, building on an earlier finding of similar vulnerabilities among parents of children with cancer, compared with parents of healthy children.

“It doesn’t matter what you search for, there is an overwhelming level of information online,” the lead author on both studies, Jeanine Guidry, PhD, from Virginia Commonwealth University’s Massey Cancer Center in Richmond, said in an interview. “If misinformation is the first thing you encounter about a topic, you’re much more likely to believe it and it’s going to be very hard to convince you otherwise.”

Before the pandemic, Dr. Guidry, who is director of the Media+Health Lab at VCU, had already been studying vaccine misinformation on Pinterest and Instagram.

So when data coming out at the start of the pandemic suggested that an increase in pediatric cancer mortality might be partially because of COVID-19 misinformation, she jumped on it.

Dr. Guidry and associates designed a questionnaire involving COVID misinformation statements available online and found that parents of children with cancer were significantly more likely to endorse them, compared with parents of healthy children.

“Our advice to clinicians is you may have an issue here,” Dr. Guidry said in an interview. “You may want to check where they get their news, and if there’s any pieces of misinformation that could be harmful.”

Some beliefs, such as eating more garlic protects against COVID, are not particularly harmful, she acknowledged, but others – such as drinking bleach being protective – are quite harmful, and they often stem from the same misinformation sources.

Both of Dr. Guidry’s studies involved surveys of either adult patients with cancer or parents of children with cancer.

The adult patient survey was conducted June 1-15, 2020, and included 897 respondents, of whom 287 were patients in active treatment for cancer, 301 were survivors not currently in treatment, and 309 had no cancer history.

The parents’ survey, conducted in May 2020, included 735 parents of children aged 2-17 years, 315 of whom had children currently undergoing cancer treatment, and 420 of whom had children with no history of cancer.

Among the misinformation they were asked to agree or disagree with were statements such as “it is unsafe to receive mail from China,” “antibiotics can prevent and treat COVID-19,” and “COVID is less deadly than the ‘flu,’ ” among others.

The surveys revealed that the patients in current treatment for cancer and the parents of patients in current treatment were most likely to endorse COVID misinformation. Results from the parents’ survey showed that “believing misinformation was also more likely for fathers, younger parents, and parents with higher perceived stress from COVID-19,” the authors wrote. Among adult patients and controls, patients in active treatment were most likely to believe misinformation, with cancer survivors no longer in treatment being the least likely to believe it, compared with healthy controls who were in between.

Why the difference? The authors suggested that patients in active treatment “may seek out more information on the internet or via social media where they are more exposed to misinformation,” whereas survivors no longer undergoing treatment may be more “media savvy and have learned to be wary of questionable health information.”

In their articles, Dr. Guidry and associates advised oncologists to be aware of their patients’ potential to endorse COVID misinformation and to “proactively address this in routine visits as well as tailored written materials.” This is easier said than done, she commented, acknowledging that keeping up with the latest misinformation is a challenge.

The misinformation statements her group used in their surveys were popular early in the pandemic, but “some of them have shown fairly remarkable staying power and some have been replaced,” she said. She invited interested clinicians to contact her team for guidance on newer misinformation.

Ultimately, she believes most patients with cancer who endorse misinformation are simply afraid, and looking for help. “They’re already dealing with a level of stress from their illness and then they’re thrown into a pandemic,” Dr. Guidry said. “At some point you just want a solution. Hydroxychloroquine? Great! Horse dewormer? Fantastic! Just wanting to control the situation and not having something else to deal with.”

Both studies were funded by the National Cancer Institute at the National Institutes of Health. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the past 2 years, oncology practitioners around the world have struggled with the same dilemma: how to maintain their patients’ cancer care without exposing them to COVID-19. Regardless of the country, language, or even which wave of the pandemic, the conversations have likely been very similar: weighing risks versuss benefits, and individualizing each patient’s pandemic cancer plan.

But one question most oncologists have probably overlooked in these discussions is about where their patients get their COVID information – or misinformation.

Surprisingly, this seemingly small detail could make a big difference in a patient’s prognosis.

A recent study found that adult cancer patients are more vulnerable to COVID misinformation, compared with healthy controls, building on an earlier finding of similar vulnerabilities among parents of children with cancer, compared with parents of healthy children.

“It doesn’t matter what you search for, there is an overwhelming level of information online,” the lead author on both studies, Jeanine Guidry, PhD, from Virginia Commonwealth University’s Massey Cancer Center in Richmond, said in an interview. “If misinformation is the first thing you encounter about a topic, you’re much more likely to believe it and it’s going to be very hard to convince you otherwise.”

Before the pandemic, Dr. Guidry, who is director of the Media+Health Lab at VCU, had already been studying vaccine misinformation on Pinterest and Instagram.

So when data coming out at the start of the pandemic suggested that an increase in pediatric cancer mortality might be partially because of COVID-19 misinformation, she jumped on it.

Dr. Guidry and associates designed a questionnaire involving COVID misinformation statements available online and found that parents of children with cancer were significantly more likely to endorse them, compared with parents of healthy children.

“Our advice to clinicians is you may have an issue here,” Dr. Guidry said in an interview. “You may want to check where they get their news, and if there’s any pieces of misinformation that could be harmful.”

Some beliefs, such as eating more garlic protects against COVID, are not particularly harmful, she acknowledged, but others – such as drinking bleach being protective – are quite harmful, and they often stem from the same misinformation sources.

Both of Dr. Guidry’s studies involved surveys of either adult patients with cancer or parents of children with cancer.

The adult patient survey was conducted June 1-15, 2020, and included 897 respondents, of whom 287 were patients in active treatment for cancer, 301 were survivors not currently in treatment, and 309 had no cancer history.

The parents’ survey, conducted in May 2020, included 735 parents of children aged 2-17 years, 315 of whom had children currently undergoing cancer treatment, and 420 of whom had children with no history of cancer.

Among the misinformation they were asked to agree or disagree with were statements such as “it is unsafe to receive mail from China,” “antibiotics can prevent and treat COVID-19,” and “COVID is less deadly than the ‘flu,’ ” among others.

The surveys revealed that the patients in current treatment for cancer and the parents of patients in current treatment were most likely to endorse COVID misinformation. Results from the parents’ survey showed that “believing misinformation was also more likely for fathers, younger parents, and parents with higher perceived stress from COVID-19,” the authors wrote. Among adult patients and controls, patients in active treatment were most likely to believe misinformation, with cancer survivors no longer in treatment being the least likely to believe it, compared with healthy controls who were in between.

Why the difference? The authors suggested that patients in active treatment “may seek out more information on the internet or via social media where they are more exposed to misinformation,” whereas survivors no longer undergoing treatment may be more “media savvy and have learned to be wary of questionable health information.”

In their articles, Dr. Guidry and associates advised oncologists to be aware of their patients’ potential to endorse COVID misinformation and to “proactively address this in routine visits as well as tailored written materials.” This is easier said than done, she commented, acknowledging that keeping up with the latest misinformation is a challenge.

The misinformation statements her group used in their surveys were popular early in the pandemic, but “some of them have shown fairly remarkable staying power and some have been replaced,” she said. She invited interested clinicians to contact her team for guidance on newer misinformation.

Ultimately, she believes most patients with cancer who endorse misinformation are simply afraid, and looking for help. “They’re already dealing with a level of stress from their illness and then they’re thrown into a pandemic,” Dr. Guidry said. “At some point you just want a solution. Hydroxychloroquine? Great! Horse dewormer? Fantastic! Just wanting to control the situation and not having something else to deal with.”

Both studies were funded by the National Cancer Institute at the National Institutes of Health. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the past 2 years, oncology practitioners around the world have struggled with the same dilemma: how to maintain their patients’ cancer care without exposing them to COVID-19. Regardless of the country, language, or even which wave of the pandemic, the conversations have likely been very similar: weighing risks versuss benefits, and individualizing each patient’s pandemic cancer plan.

But one question most oncologists have probably overlooked in these discussions is about where their patients get their COVID information – or misinformation.

Surprisingly, this seemingly small detail could make a big difference in a patient’s prognosis.

A recent study found that adult cancer patients are more vulnerable to COVID misinformation, compared with healthy controls, building on an earlier finding of similar vulnerabilities among parents of children with cancer, compared with parents of healthy children.

“It doesn’t matter what you search for, there is an overwhelming level of information online,” the lead author on both studies, Jeanine Guidry, PhD, from Virginia Commonwealth University’s Massey Cancer Center in Richmond, said in an interview. “If misinformation is the first thing you encounter about a topic, you’re much more likely to believe it and it’s going to be very hard to convince you otherwise.”

Before the pandemic, Dr. Guidry, who is director of the Media+Health Lab at VCU, had already been studying vaccine misinformation on Pinterest and Instagram.

So when data coming out at the start of the pandemic suggested that an increase in pediatric cancer mortality might be partially because of COVID-19 misinformation, she jumped on it.

Dr. Guidry and associates designed a questionnaire involving COVID misinformation statements available online and found that parents of children with cancer were significantly more likely to endorse them, compared with parents of healthy children.

“Our advice to clinicians is you may have an issue here,” Dr. Guidry said in an interview. “You may want to check where they get their news, and if there’s any pieces of misinformation that could be harmful.”

Some beliefs, such as eating more garlic protects against COVID, are not particularly harmful, she acknowledged, but others – such as drinking bleach being protective – are quite harmful, and they often stem from the same misinformation sources.

Both of Dr. Guidry’s studies involved surveys of either adult patients with cancer or parents of children with cancer.

The adult patient survey was conducted June 1-15, 2020, and included 897 respondents, of whom 287 were patients in active treatment for cancer, 301 were survivors not currently in treatment, and 309 had no cancer history.

The parents’ survey, conducted in May 2020, included 735 parents of children aged 2-17 years, 315 of whom had children currently undergoing cancer treatment, and 420 of whom had children with no history of cancer.

Among the misinformation they were asked to agree or disagree with were statements such as “it is unsafe to receive mail from China,” “antibiotics can prevent and treat COVID-19,” and “COVID is less deadly than the ‘flu,’ ” among others.

The surveys revealed that the patients in current treatment for cancer and the parents of patients in current treatment were most likely to endorse COVID misinformation. Results from the parents’ survey showed that “believing misinformation was also more likely for fathers, younger parents, and parents with higher perceived stress from COVID-19,” the authors wrote. Among adult patients and controls, patients in active treatment were most likely to believe misinformation, with cancer survivors no longer in treatment being the least likely to believe it, compared with healthy controls who were in between.

Why the difference? The authors suggested that patients in active treatment “may seek out more information on the internet or via social media where they are more exposed to misinformation,” whereas survivors no longer undergoing treatment may be more “media savvy and have learned to be wary of questionable health information.”

In their articles, Dr. Guidry and associates advised oncologists to be aware of their patients’ potential to endorse COVID misinformation and to “proactively address this in routine visits as well as tailored written materials.” This is easier said than done, she commented, acknowledging that keeping up with the latest misinformation is a challenge.

The misinformation statements her group used in their surveys were popular early in the pandemic, but “some of them have shown fairly remarkable staying power and some have been replaced,” she said. She invited interested clinicians to contact her team for guidance on newer misinformation.

Ultimately, she believes most patients with cancer who endorse misinformation are simply afraid, and looking for help. “They’re already dealing with a level of stress from their illness and then they’re thrown into a pandemic,” Dr. Guidry said. “At some point you just want a solution. Hydroxychloroquine? Great! Horse dewormer? Fantastic! Just wanting to control the situation and not having something else to deal with.”

Both studies were funded by the National Cancer Institute at the National Institutes of Health. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The endocannabinoid system is a promising therapeutic target for the treatment of migraine, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.

Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
 

Not just cannabis

In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.

The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”

Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.

There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.

Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.

Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.

“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
 

Patients are taking cannabinoids; physicians should learn about them

Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.

“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”

The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.

The endocannabinoid system is a promising therapeutic target for the treatment of migraine, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.

Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
 

Not just cannabis

In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.

The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”

Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.

There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.

Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.

Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.

“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
 

Patients are taking cannabinoids; physicians should learn about them

Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.

“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”

The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.

The endocannabinoid system is a promising therapeutic target for the treatment of migraine, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.

Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
 

Not just cannabis

In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.

The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”

Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.

There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.

Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.

Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.

“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
 

Patients are taking cannabinoids; physicians should learn about them

Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.

“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”

The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.

Women with physical, intellectual, and sensory disabilities had higher risk for almost all pregnancy complications, obstetric interventions, and adverse outcomes, including severe maternal morbidity (SMM) and mortality compared to women without disabilities, according to an analysis of a large, retrospective cohort.

The findings, published in JAMA Network Open (2021;4[12]:e2138414 doi: 10.1001/jamanetworkopen.2021.38414), “may be a direct reflection of the challenges women with all types of disabilities face when accessing and receiving care, which is likely compounded by poorer preconception health,” suggested lead author Jessica L. Gleason, PhD, MPH, and co-authors, all from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.

“Women with disabilities have long been ignored in obstetric research and clinical practice,” added Hilary K. Brown, PhD, from the University of Toronto, in an accompanying editorial. “Inclusion of disability indicators needs to be the norm – not the exception – in health administrative data so that these disparities can be regularly tracked and addressed.”

The investigators used data from the Consortium on Safe Labor (CSL), a retrospective cohort of deliveries from 12 U.S. clinical centers between Jan. 2002 and Jan. 2008, to analyze obstetric interventions and adverse maternal outcomes in women with and without disabilities.

The analysis included a total of 223,385 women, mean age 27.6 years, of whom 2,074 (0.9%) had a disability, and 221,311 did not. Among those with disabilities, 1,733 (83.5%) were physical, 91 (4.4%) were intellectual, and 250 (12.1%) were sensory. While almost half (49.4%) of the women were White, 22.5% were Black, 17.5% were Hispanic, and 4.1% were Asian or Pacific Islander.

Outcomes were analyzed with three composite measures:

• Pregnancy-related complications (pregnancy-related hypertensive diseases, gestational diabetes, placental abruption, placenta previa, premature rupture of membranes, preterm PROM);
• All labor, delivery, and postpartum complications (chorioamnionitis, hemorrhage, blood transfusion, thromboembolism, postpartum fever, infection, cardiovascular events, cardiomyopathy, and maternal death);
• SMM only, including severe pre-eclampsia/eclampsia, hemorrhage, thromboembolism, fever, infection, cardiomyopathy, and cardiovascular events during labor and delivery.

After adjustment for covariates, women with disabilities had higher risk of pregnancy-related complications. This included a 48% higher risk of mild pre-eclampsia and double the risk of severe pre-eclampsia/eclampsia. The composite risk of any pregnancy complication was 27% higher for women with physical disabilities, 49% higher for women with intellectual disabilities, and 53% higher for women with sensory disabilities.

The findings were similar for labor, delivery, and postpartum complications, showing women with disabilities had higher risk for a range of obstetrical interventions, including cesarean delivery – both planned and intrapartum (aRR, 1.34). Additionally, women with disabilities were less likely to have a cesarean delivery that was “solely clinically indicated” (aRR, 0.79), and more likely to have a cesarean delivery for “softer” mixed indication (aRR, 1.16), “supporting a possible overuse of cesarean delivery among women with disability,” they suggested.

Women with disabilities also had a higher risk of postpartum hemorrhage (aRR, 1.27), blood transfusion (aRR, 1.64), and maternal mortality (aRR, 11.19), as well as individual markers of severe maternal morbidity, such as cardiovascular events (aRR, 4.02), infection (aRR, 2.69), and venous thromboembolism (aRR, 6.08).

The authors speculate that the increased risks for women with disabilities “may be the result of a combination of independent risk factors, including the higher rate of obstetric intervention via cesarean delivery, under-recognition of women with disabilities as a population with higher-risk pregnancies, and lack of health care practitioner knowledge or comfort in managing pregnancies among women with disabilities.”

Dr. Brown noted in her commentary that there is a need for better education of health care professionals in this area. “Given that 12% of reproductive-aged women have a disability, that pregnancy rates are similar among women with and without disabilities, and that women with disabilities are at elevated risk of a range of adverse maternal outcomes, including severe maternal morbidity and maternal mortality, disability modules should be a mandatory component of education for obstetricians and midwives as well as other obstetrical health care professionals.”

Calling the study “a serious wake-up call,” Monika Mitra, PhD, told this publication that the findings highlight the need for “urgent attention” on improving obstetric care for people with disabilities “with a focus on accessibility and inclusion, changing clinical practice to better serve disabled people, integrating disability-related training for health care practitioners, and developing evidence-based interventions to support people with disabilities during this time.” The associate professor and director of the Lurie Institute for Disability Policy, in Brandeis University, Waltham, Mass. said the risk factors for poor outcomes are present early in pregnancy or even preconception. “We know that disabled women report barriers in accessing health care and receive lower-quality care compared to nondisabled women and are more likely to experience poverty, housing and food insecurity, educational and employment barriers, abuse, chronic health conditions, and mental illness than women without disabilities.”

She noted that the study’s sample of people with disabilities was small, and the measure of disability used was based on ICD-9 codes, which captures only severe disabilities. “As noted in the commentary by [Dr.] Brown, our standard sources of health administrative data do not give us the full picture on disability, and we need other, more equitable ways of identifying disability based, for example, on self-reports of activity or participation limitations if we are to be able to understand the effects on obstetric outcomes of health and health care disparities and of social determinants of health. Moreover, researchers have generally not yet begun to incorporate knowledge of the experiences of transgender people during pregnancy, which will impact our measures and study of obstetric outcomes among people with disabilities as well as the language we use.”

The study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study authors and Dr. Brown reported no conflicts of interest. Dr. Mitra receives funding from the NICHD and the National Institute on Disability, Independent Living for research on pregnancy outcomes among people with disabilities.

obnews@mdedge.com

Women with physical, intellectual, and sensory disabilities had higher risk for almost all pregnancy complications, obstetric interventions, and adverse outcomes, including severe maternal morbidity (SMM) and mortality compared to women without disabilities, according to an analysis of a large, retrospective cohort.

The findings, published in JAMA Network Open (2021;4[12]:e2138414 doi: 10.1001/jamanetworkopen.2021.38414), “may be a direct reflection of the challenges women with all types of disabilities face when accessing and receiving care, which is likely compounded by poorer preconception health,” suggested lead author Jessica L. Gleason, PhD, MPH, and co-authors, all from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.

“Women with disabilities have long been ignored in obstetric research and clinical practice,” added Hilary K. Brown, PhD, from the University of Toronto, in an accompanying editorial. “Inclusion of disability indicators needs to be the norm – not the exception – in health administrative data so that these disparities can be regularly tracked and addressed.”

The investigators used data from the Consortium on Safe Labor (CSL), a retrospective cohort of deliveries from 12 U.S. clinical centers between Jan. 2002 and Jan. 2008, to analyze obstetric interventions and adverse maternal outcomes in women with and without disabilities.

The analysis included a total of 223,385 women, mean age 27.6 years, of whom 2,074 (0.9%) had a disability, and 221,311 did not. Among those with disabilities, 1,733 (83.5%) were physical, 91 (4.4%) were intellectual, and 250 (12.1%) were sensory. While almost half (49.4%) of the women were White, 22.5% were Black, 17.5% were Hispanic, and 4.1% were Asian or Pacific Islander.

Outcomes were analyzed with three composite measures:

• Pregnancy-related complications (pregnancy-related hypertensive diseases, gestational diabetes, placental abruption, placenta previa, premature rupture of membranes, preterm PROM);
• All labor, delivery, and postpartum complications (chorioamnionitis, hemorrhage, blood transfusion, thromboembolism, postpartum fever, infection, cardiovascular events, cardiomyopathy, and maternal death);
• SMM only, including severe pre-eclampsia/eclampsia, hemorrhage, thromboembolism, fever, infection, cardiomyopathy, and cardiovascular events during labor and delivery.

After adjustment for covariates, women with disabilities had higher risk of pregnancy-related complications. This included a 48% higher risk of mild pre-eclampsia and double the risk of severe pre-eclampsia/eclampsia. The composite risk of any pregnancy complication was 27% higher for women with physical disabilities, 49% higher for women with intellectual disabilities, and 53% higher for women with sensory disabilities.

The findings were similar for labor, delivery, and postpartum complications, showing women with disabilities had higher risk for a range of obstetrical interventions, including cesarean delivery – both planned and intrapartum (aRR, 1.34). Additionally, women with disabilities were less likely to have a cesarean delivery that was “solely clinically indicated” (aRR, 0.79), and more likely to have a cesarean delivery for “softer” mixed indication (aRR, 1.16), “supporting a possible overuse of cesarean delivery among women with disability,” they suggested.

Women with disabilities also had a higher risk of postpartum hemorrhage (aRR, 1.27), blood transfusion (aRR, 1.64), and maternal mortality (aRR, 11.19), as well as individual markers of severe maternal morbidity, such as cardiovascular events (aRR, 4.02), infection (aRR, 2.69), and venous thromboembolism (aRR, 6.08).

The authors speculate that the increased risks for women with disabilities “may be the result of a combination of independent risk factors, including the higher rate of obstetric intervention via cesarean delivery, under-recognition of women with disabilities as a population with higher-risk pregnancies, and lack of health care practitioner knowledge or comfort in managing pregnancies among women with disabilities.”

Dr. Brown noted in her commentary that there is a need for better education of health care professionals in this area. “Given that 12% of reproductive-aged women have a disability, that pregnancy rates are similar among women with and without disabilities, and that women with disabilities are at elevated risk of a range of adverse maternal outcomes, including severe maternal morbidity and maternal mortality, disability modules should be a mandatory component of education for obstetricians and midwives as well as other obstetrical health care professionals.”

Calling the study “a serious wake-up call,” Monika Mitra, PhD, told this publication that the findings highlight the need for “urgent attention” on improving obstetric care for people with disabilities “with a focus on accessibility and inclusion, changing clinical practice to better serve disabled people, integrating disability-related training for health care practitioners, and developing evidence-based interventions to support people with disabilities during this time.” The associate professor and director of the Lurie Institute for Disability Policy, in Brandeis University, Waltham, Mass. said the risk factors for poor outcomes are present early in pregnancy or even preconception. “We know that disabled women report barriers in accessing health care and receive lower-quality care compared to nondisabled women and are more likely to experience poverty, housing and food insecurity, educational and employment barriers, abuse, chronic health conditions, and mental illness than women without disabilities.”

She noted that the study’s sample of people with disabilities was small, and the measure of disability used was based on ICD-9 codes, which captures only severe disabilities. “As noted in the commentary by [Dr.] Brown, our standard sources of health administrative data do not give us the full picture on disability, and we need other, more equitable ways of identifying disability based, for example, on self-reports of activity or participation limitations if we are to be able to understand the effects on obstetric outcomes of health and health care disparities and of social determinants of health. Moreover, researchers have generally not yet begun to incorporate knowledge of the experiences of transgender people during pregnancy, which will impact our measures and study of obstetric outcomes among people with disabilities as well as the language we use.”

The study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study authors and Dr. Brown reported no conflicts of interest. Dr. Mitra receives funding from the NICHD and the National Institute on Disability, Independent Living for research on pregnancy outcomes among people with disabilities.

obnews@mdedge.com

Women with physical, intellectual, and sensory disabilities had higher risk for almost all pregnancy complications, obstetric interventions, and adverse outcomes, including severe maternal morbidity (SMM) and mortality compared to women without disabilities, according to an analysis of a large, retrospective cohort.

The findings, published in JAMA Network Open (2021;4[12]:e2138414 doi: 10.1001/jamanetworkopen.2021.38414), “may be a direct reflection of the challenges women with all types of disabilities face when accessing and receiving care, which is likely compounded by poorer preconception health,” suggested lead author Jessica L. Gleason, PhD, MPH, and co-authors, all from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.

“Women with disabilities have long been ignored in obstetric research and clinical practice,” added Hilary K. Brown, PhD, from the University of Toronto, in an accompanying editorial. “Inclusion of disability indicators needs to be the norm – not the exception – in health administrative data so that these disparities can be regularly tracked and addressed.”

The investigators used data from the Consortium on Safe Labor (CSL), a retrospective cohort of deliveries from 12 U.S. clinical centers between Jan. 2002 and Jan. 2008, to analyze obstetric interventions and adverse maternal outcomes in women with and without disabilities.

The analysis included a total of 223,385 women, mean age 27.6 years, of whom 2,074 (0.9%) had a disability, and 221,311 did not. Among those with disabilities, 1,733 (83.5%) were physical, 91 (4.4%) were intellectual, and 250 (12.1%) were sensory. While almost half (49.4%) of the women were White, 22.5% were Black, 17.5% were Hispanic, and 4.1% were Asian or Pacific Islander.

Outcomes were analyzed with three composite measures:

• Pregnancy-related complications (pregnancy-related hypertensive diseases, gestational diabetes, placental abruption, placenta previa, premature rupture of membranes, preterm PROM);
• All labor, delivery, and postpartum complications (chorioamnionitis, hemorrhage, blood transfusion, thromboembolism, postpartum fever, infection, cardiovascular events, cardiomyopathy, and maternal death);
• SMM only, including severe pre-eclampsia/eclampsia, hemorrhage, thromboembolism, fever, infection, cardiomyopathy, and cardiovascular events during labor and delivery.

After adjustment for covariates, women with disabilities had higher risk of pregnancy-related complications. This included a 48% higher risk of mild pre-eclampsia and double the risk of severe pre-eclampsia/eclampsia. The composite risk of any pregnancy complication was 27% higher for women with physical disabilities, 49% higher for women with intellectual disabilities, and 53% higher for women with sensory disabilities.

The findings were similar for labor, delivery, and postpartum complications, showing women with disabilities had higher risk for a range of obstetrical interventions, including cesarean delivery – both planned and intrapartum (aRR, 1.34). Additionally, women with disabilities were less likely to have a cesarean delivery that was “solely clinically indicated” (aRR, 0.79), and more likely to have a cesarean delivery for “softer” mixed indication (aRR, 1.16), “supporting a possible overuse of cesarean delivery among women with disability,” they suggested.

Women with disabilities also had a higher risk of postpartum hemorrhage (aRR, 1.27), blood transfusion (aRR, 1.64), and maternal mortality (aRR, 11.19), as well as individual markers of severe maternal morbidity, such as cardiovascular events (aRR, 4.02), infection (aRR, 2.69), and venous thromboembolism (aRR, 6.08).

The authors speculate that the increased risks for women with disabilities “may be the result of a combination of independent risk factors, including the higher rate of obstetric intervention via cesarean delivery, under-recognition of women with disabilities as a population with higher-risk pregnancies, and lack of health care practitioner knowledge or comfort in managing pregnancies among women with disabilities.”

Dr. Brown noted in her commentary that there is a need for better education of health care professionals in this area. “Given that 12% of reproductive-aged women have a disability, that pregnancy rates are similar among women with and without disabilities, and that women with disabilities are at elevated risk of a range of adverse maternal outcomes, including severe maternal morbidity and maternal mortality, disability modules should be a mandatory component of education for obstetricians and midwives as well as other obstetrical health care professionals.”

Calling the study “a serious wake-up call,” Monika Mitra, PhD, told this publication that the findings highlight the need for “urgent attention” on improving obstetric care for people with disabilities “with a focus on accessibility and inclusion, changing clinical practice to better serve disabled people, integrating disability-related training for health care practitioners, and developing evidence-based interventions to support people with disabilities during this time.” The associate professor and director of the Lurie Institute for Disability Policy, in Brandeis University, Waltham, Mass. said the risk factors for poor outcomes are present early in pregnancy or even preconception. “We know that disabled women report barriers in accessing health care and receive lower-quality care compared to nondisabled women and are more likely to experience poverty, housing and food insecurity, educational and employment barriers, abuse, chronic health conditions, and mental illness than women without disabilities.”

She noted that the study’s sample of people with disabilities was small, and the measure of disability used was based on ICD-9 codes, which captures only severe disabilities. “As noted in the commentary by [Dr.] Brown, our standard sources of health administrative data do not give us the full picture on disability, and we need other, more equitable ways of identifying disability based, for example, on self-reports of activity or participation limitations if we are to be able to understand the effects on obstetric outcomes of health and health care disparities and of social determinants of health. Moreover, researchers have generally not yet begun to incorporate knowledge of the experiences of transgender people during pregnancy, which will impact our measures and study of obstetric outcomes among people with disabilities as well as the language we use.”

The study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study authors and Dr. Brown reported no conflicts of interest. Dr. Mitra receives funding from the NICHD and the National Institute on Disability, Independent Living for research on pregnancy outcomes among people with disabilities.

obnews@mdedge.com

When it comes to the acute management of migraines, newer is not necessarily better, according to an analysis of studies comparing triptans – the standard of care – to two newer classifications of medications. The findings, published in JAMA Network Open, “may imply that triptans will remain the current mainstay of specific acute migraine treatment,” suggested senior author Shuu-Jiun Wang, MD, from the National Yang Ming Chiao Tung University, and the Taipei Veterans General Hospital, both in Taipei, Taiwan, and his coauthors. However, lasmiditan (a 5-hydroxytryptamine_1F receptor agonist) and rimegepant and ubrogepant (both calcitonin gene-related peptide [CGRP] antagonists) might still have unique advantages, since triptans are contraindicated for patients with cardiovascular risks, they said.

The systemic review and meta-analysis showed that, for the outcome of pain freedom and pain relief at 2 hours after the dose, the three newer agents worked better than placebo, but were inferior to most triptans. However, ubrogepant and rimegepant, which received U.S. Food and Drug Administration approval for the treatment of acute migraine in adults in December 2019 and February 2020, respectively, might be associated with fewer risks of adverse events (AEs), compared with triptans. “These new effective therapeutic options enrich the therapeutic categories of specific acute migraine treatments and may provide an opportunity to decrease the risks of barbiturate or opioid overuse or addiction,” they wrote.

The meta-analysis included 64 randomized, controlled trials involving 46,442 participants (74%-87% female across studies; age range, 36-43 years). All studies examined clinically relevant outcomes in patients with International Headache Society criteria for migraine, and compared currently available migraine-specific acute treatments with each other or placebo. The drugs were examined at doses with widespread clinical use and included: ergotamine, dihydroergotamine, sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, frovatriptan, lasmiditan, rimegepant, and ubrogepant.

The findings showed that all drug treatments were associated with a higher odds ratio for pain freedom, compared with placebo, except for sumatriptan, 10-mg nasal spray. The most effective drug was eletriptan 40 mg (OR, 5.59), and the least effective was lasmiditan 50 mg (OR, 1.65). Most triptans were associated with higher ORs for both pain freedom and pain relief at 2 hours, compared with lasmiditan, rimegepant, or ubrogepant, while comparisons between lasmiditan, rimegepant, and ubrogepant for these outcomes showed no statistically significant difference, they reported.

Lasmiditan was associated with the highest risk of any AEs, “however, the AEs were tolerable and were not considered serious. … Therefore, we suggest that the benefits should be weighed against the risk of its AEs when considering the clinical application of lasmiditan,” they wrote. Certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any AEs, compared with the CGRP antagonists. “Nevertheless, most of the AEs were mild to moderate, and the percentages of serious AEs were low (0.0%-2.1%).”

Finally, the authors noted that their observations of successful treatment with 5-hydroxytriptamine_1F receptor agonists and CGRP antagonists “reveals that vasoconstriction is not essential for antimigraine therapy.” which could have implications for future pharmaceutical development.
 

Older and newer medications each have advantages

“Triptans will be around for a long time, but the newer medications are here to stay,” said Alan M. Rapoport, MD, in reaction to the study. “Before this publication, we knew that the 2-hour efficacy results of the newer medications were not quite as good as the faster-acting triptans; and after this network meta-analysis we are more sure of that,” said Dr. Rapoport, of the department of neurology at University of California, Los Angeles. “But the fact that the three newer medications do not constrict blood vessels and can easily be given even to patients with contraindications to triptans, or patients that simply are at greater risk due to obesity, smoking history, family history, diabetes, lack of exercise, or higher lipid levels, puts them into a desirable category.”

Calling it a “very carefully done” systematic review, Dr. Rapoport had a few caveats about the strength of the research. The trials that were included were not identically designed and were performed in different areas, by different investigators, on different patients, he noted. They were also not head-to-head trials “which ensures that the resultant data are more pure.” The studies also looked only at rapid results at 2 hours after dosing. “In my experience, patients are often satisfied with the response times from these newer agents; and doctors and patients both are happy that they are not vasoconstrictive,” he said. “The researchers also omitted studies looking at zolmitriptan nasal spray, which I have found to be rapid in onset and efficacious with few adverse events.”

Finally, Dr. Rapoport noted that one condition not examined in the review was medication overuse headache (MOH), which is “a major problem with patients that have high-frequency episodic migraine and chronic migraine. To our knowledge thus far, the two gepants (ubrogepant and rimegepant) do not appear to cause MOH when taken frequently, and these agents may end up being a treatment for this condition.”

Dr Wang reported receiving personal fees from Eli Lilly, Daiichi-Sankyo, Norvatis Taiwan, Biogen, Pfizer, and Bayer; and grants from AbbVie, Norvatis, Eli Lilly, Taiwan Ministry of Technology and Science, Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. No other disclosures were reported. Dr. Rapoport serves as an advisor for AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano; he is on the Speakers Bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries. He is Editor-in-Chief of Neurology Reviews.

The study was funded by the Ministry of Science and Technology, Taiwan, Ministry of Education, Taiwan, and the Brain Research Center, National Yang Ming Chiao Tung University.

When it comes to the acute management of migraines, newer is not necessarily better, according to an analysis of studies comparing triptans – the standard of care – to two newer classifications of medications. The findings, published in JAMA Network Open, “may imply that triptans will remain the current mainstay of specific acute migraine treatment,” suggested senior author Shuu-Jiun Wang, MD, from the National Yang Ming Chiao Tung University, and the Taipei Veterans General Hospital, both in Taipei, Taiwan, and his coauthors. However, lasmiditan (a 5-hydroxytryptamine_1F receptor agonist) and rimegepant and ubrogepant (both calcitonin gene-related peptide [CGRP] antagonists) might still have unique advantages, since triptans are contraindicated for patients with cardiovascular risks, they said.

The systemic review and meta-analysis showed that, for the outcome of pain freedom and pain relief at 2 hours after the dose, the three newer agents worked better than placebo, but were inferior to most triptans. However, ubrogepant and rimegepant, which received U.S. Food and Drug Administration approval for the treatment of acute migraine in adults in December 2019 and February 2020, respectively, might be associated with fewer risks of adverse events (AEs), compared with triptans. “These new effective therapeutic options enrich the therapeutic categories of specific acute migraine treatments and may provide an opportunity to decrease the risks of barbiturate or opioid overuse or addiction,” they wrote.

The meta-analysis included 64 randomized, controlled trials involving 46,442 participants (74%-87% female across studies; age range, 36-43 years). All studies examined clinically relevant outcomes in patients with International Headache Society criteria for migraine, and compared currently available migraine-specific acute treatments with each other or placebo. The drugs were examined at doses with widespread clinical use and included: ergotamine, dihydroergotamine, sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, frovatriptan, lasmiditan, rimegepant, and ubrogepant.

The findings showed that all drug treatments were associated with a higher odds ratio for pain freedom, compared with placebo, except for sumatriptan, 10-mg nasal spray. The most effective drug was eletriptan 40 mg (OR, 5.59), and the least effective was lasmiditan 50 mg (OR, 1.65). Most triptans were associated with higher ORs for both pain freedom and pain relief at 2 hours, compared with lasmiditan, rimegepant, or ubrogepant, while comparisons between lasmiditan, rimegepant, and ubrogepant for these outcomes showed no statistically significant difference, they reported.

Lasmiditan was associated with the highest risk of any AEs, “however, the AEs were tolerable and were not considered serious. … Therefore, we suggest that the benefits should be weighed against the risk of its AEs when considering the clinical application of lasmiditan,” they wrote. Certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any AEs, compared with the CGRP antagonists. “Nevertheless, most of the AEs were mild to moderate, and the percentages of serious AEs were low (0.0%-2.1%).”

Finally, the authors noted that their observations of successful treatment with 5-hydroxytriptamine_1F receptor agonists and CGRP antagonists “reveals that vasoconstriction is not essential for antimigraine therapy.” which could have implications for future pharmaceutical development.
 

Older and newer medications each have advantages

“Triptans will be around for a long time, but the newer medications are here to stay,” said Alan M. Rapoport, MD, in reaction to the study. “Before this publication, we knew that the 2-hour efficacy results of the newer medications were not quite as good as the faster-acting triptans; and after this network meta-analysis we are more sure of that,” said Dr. Rapoport, of the department of neurology at University of California, Los Angeles. “But the fact that the three newer medications do not constrict blood vessels and can easily be given even to patients with contraindications to triptans, or patients that simply are at greater risk due to obesity, smoking history, family history, diabetes, lack of exercise, or higher lipid levels, puts them into a desirable category.”

Calling it a “very carefully done” systematic review, Dr. Rapoport had a few caveats about the strength of the research. The trials that were included were not identically designed and were performed in different areas, by different investigators, on different patients, he noted. They were also not head-to-head trials “which ensures that the resultant data are more pure.” The studies also looked only at rapid results at 2 hours after dosing. “In my experience, patients are often satisfied with the response times from these newer agents; and doctors and patients both are happy that they are not vasoconstrictive,” he said. “The researchers also omitted studies looking at zolmitriptan nasal spray, which I have found to be rapid in onset and efficacious with few adverse events.”

Finally, Dr. Rapoport noted that one condition not examined in the review was medication overuse headache (MOH), which is “a major problem with patients that have high-frequency episodic migraine and chronic migraine. To our knowledge thus far, the two gepants (ubrogepant and rimegepant) do not appear to cause MOH when taken frequently, and these agents may end up being a treatment for this condition.”

Dr Wang reported receiving personal fees from Eli Lilly, Daiichi-Sankyo, Norvatis Taiwan, Biogen, Pfizer, and Bayer; and grants from AbbVie, Norvatis, Eli Lilly, Taiwan Ministry of Technology and Science, Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. No other disclosures were reported. Dr. Rapoport serves as an advisor for AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano; he is on the Speakers Bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries. He is Editor-in-Chief of Neurology Reviews.

The study was funded by the Ministry of Science and Technology, Taiwan, Ministry of Education, Taiwan, and the Brain Research Center, National Yang Ming Chiao Tung University.

When it comes to the acute management of migraines, newer is not necessarily better, according to an analysis of studies comparing triptans – the standard of care – to two newer classifications of medications. The findings, published in JAMA Network Open, “may imply that triptans will remain the current mainstay of specific acute migraine treatment,” suggested senior author Shuu-Jiun Wang, MD, from the National Yang Ming Chiao Tung University, and the Taipei Veterans General Hospital, both in Taipei, Taiwan, and his coauthors. However, lasmiditan (a 5-hydroxytryptamine_1F receptor agonist) and rimegepant and ubrogepant (both calcitonin gene-related peptide [CGRP] antagonists) might still have unique advantages, since triptans are contraindicated for patients with cardiovascular risks, they said.

The systemic review and meta-analysis showed that, for the outcome of pain freedom and pain relief at 2 hours after the dose, the three newer agents worked better than placebo, but were inferior to most triptans. However, ubrogepant and rimegepant, which received U.S. Food and Drug Administration approval for the treatment of acute migraine in adults in December 2019 and February 2020, respectively, might be associated with fewer risks of adverse events (AEs), compared with triptans. “These new effective therapeutic options enrich the therapeutic categories of specific acute migraine treatments and may provide an opportunity to decrease the risks of barbiturate or opioid overuse or addiction,” they wrote.

The meta-analysis included 64 randomized, controlled trials involving 46,442 participants (74%-87% female across studies; age range, 36-43 years). All studies examined clinically relevant outcomes in patients with International Headache Society criteria for migraine, and compared currently available migraine-specific acute treatments with each other or placebo. The drugs were examined at doses with widespread clinical use and included: ergotamine, dihydroergotamine, sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, frovatriptan, lasmiditan, rimegepant, and ubrogepant.

The findings showed that all drug treatments were associated with a higher odds ratio for pain freedom, compared with placebo, except for sumatriptan, 10-mg nasal spray. The most effective drug was eletriptan 40 mg (OR, 5.59), and the least effective was lasmiditan 50 mg (OR, 1.65). Most triptans were associated with higher ORs for both pain freedom and pain relief at 2 hours, compared with lasmiditan, rimegepant, or ubrogepant, while comparisons between lasmiditan, rimegepant, and ubrogepant for these outcomes showed no statistically significant difference, they reported.

Lasmiditan was associated with the highest risk of any AEs, “however, the AEs were tolerable and were not considered serious. … Therefore, we suggest that the benefits should be weighed against the risk of its AEs when considering the clinical application of lasmiditan,” they wrote. Certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any AEs, compared with the CGRP antagonists. “Nevertheless, most of the AEs were mild to moderate, and the percentages of serious AEs were low (0.0%-2.1%).”

Finally, the authors noted that their observations of successful treatment with 5-hydroxytriptamine_1F receptor agonists and CGRP antagonists “reveals that vasoconstriction is not essential for antimigraine therapy.” which could have implications for future pharmaceutical development.
 

Older and newer medications each have advantages

“Triptans will be around for a long time, but the newer medications are here to stay,” said Alan M. Rapoport, MD, in reaction to the study. “Before this publication, we knew that the 2-hour efficacy results of the newer medications were not quite as good as the faster-acting triptans; and after this network meta-analysis we are more sure of that,” said Dr. Rapoport, of the department of neurology at University of California, Los Angeles. “But the fact that the three newer medications do not constrict blood vessels and can easily be given even to patients with contraindications to triptans, or patients that simply are at greater risk due to obesity, smoking history, family history, diabetes, lack of exercise, or higher lipid levels, puts them into a desirable category.”

Calling it a “very carefully done” systematic review, Dr. Rapoport had a few caveats about the strength of the research. The trials that were included were not identically designed and were performed in different areas, by different investigators, on different patients, he noted. They were also not head-to-head trials “which ensures that the resultant data are more pure.” The studies also looked only at rapid results at 2 hours after dosing. “In my experience, patients are often satisfied with the response times from these newer agents; and doctors and patients both are happy that they are not vasoconstrictive,” he said. “The researchers also omitted studies looking at zolmitriptan nasal spray, which I have found to be rapid in onset and efficacious with few adverse events.”

Finally, Dr. Rapoport noted that one condition not examined in the review was medication overuse headache (MOH), which is “a major problem with patients that have high-frequency episodic migraine and chronic migraine. To our knowledge thus far, the two gepants (ubrogepant and rimegepant) do not appear to cause MOH when taken frequently, and these agents may end up being a treatment for this condition.”

Dr Wang reported receiving personal fees from Eli Lilly, Daiichi-Sankyo, Norvatis Taiwan, Biogen, Pfizer, and Bayer; and grants from AbbVie, Norvatis, Eli Lilly, Taiwan Ministry of Technology and Science, Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. No other disclosures were reported. Dr. Rapoport serves as an advisor for AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano; he is on the Speakers Bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries. He is Editor-in-Chief of Neurology Reviews.

The study was funded by the Ministry of Science and Technology, Taiwan, Ministry of Education, Taiwan, and the Brain Research Center, National Yang Ming Chiao Tung University.

Abortion rates remained stable and adverse events were rare after removal of mifepristone prescribing restrictions in Canada, a new study shows.

“Our study is a signal to other countries that restrictions are not necessary to ensure patient safety,” senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a press release.

“This is the strongest evidence yet that it is safe to provide the abortion pill like most other prescriptions – meaning any doctor or nurse practitioner can prescribe, any pharmacist can dispense, and patients can take the pills if, when, and where they choose,” said lead author Laura Schummers, ScD, a postdoctoral fellow in the same department.

The findings “add to the accumulating evidence that removing restrictions from medication abortion is safe, effective, and improves access,” agreed Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, who was not part of the research team. “This is additional confirmation that it is safe for patients to receive abortion care medications in the ‘normal’ fashion, through a prescription available at a pharmacy,” she said in an interview.

The study, published in the New England Journal of Medicine, compared medical abortion use, safety, and effectiveness in the province of Ontario before the Canadian availability of mifepristone and after it became available without restrictions that are similar to the Risk Evaluation and Mitigation Strategy (REMS) restrictions in place for mifepristone in the United States.

Using linked administrative health data, the researchers created a population-based cohort of all Ontario residents aged 12-49 years who had received abortion services during the study period. In total, 195,183 abortions were performed in the period before mifepristone was approved (January 2012–December 2016), and 84,032 were performed after it was made available without restrictions (Nov. 7, 2017, through March 15, 2020). The vast majority of these abortions (89.3%) were surgical, with about 10% being medically induced, the authors reported.

The study found that, while the overall abortion rate declined over the study period (from 11.9 to 11.3 per 1,000 female residents), the proportion of medical abortions jumped sharply from 2.2% to 31.4%, and the rate of second-trimester abortions declined from 5.5% of all abortions to 5.1%.

Abortion safety outcomes within 6 weeks of abortion remained stable over the two study periods. This included severe adverse events (0.03% vs. 0.04%) such as blood transfusions, abdominal surgery, admission to an ICU, or sepsis during an abortion-related hospitalization; and complications (0.74% vs. 0.69%,) such as genital tract or pelvic infection, hemorrhage, embolism, shock, renal failure, damage to pelvic organs or tissues, and venous complications among other things.

There were slight declines in overall abortion effectiveness, but ongoing pregnancy rates “remained infrequent,” the authors noted. While there was a modest rise in the rates of subsequent uterine evacuation (from 1.0% to 2.2%), and ongoing intrauterine pregnancy continuing until delivery (from 0.03% to 0.08%), the rate of ectopic pregnancy diagnosed within 6 weeks after the abortion date remained stable (from 0.15% to 0.22%).

Canada was the first country in the world to remove all supplemental restrictions on the dispensing and administration of mifepristone, according to the press release. And while professional organizations have called for the removal of such restrictions “because they impede access to abortion services without improving safety,” high-quality data on this are lacking, they added.

The study’s finding are consistent with existing U.S. and U.K. data showing Food and Drug Administration REMS restrictions requiring abortion care medications to be dispensed in a clinic by a certified provider “are unnecessary and create obstacles to early abortion access,” said Dr. Espey. “For clinicians and patients in the U.S., it’s important to note that the increasing number of legislative restrictions on abortion, including medication abortion, are non–evidence based. Politically motivated false claims of safety concerns are countered by this study and others conducted during the pandemic when both the U.S. and U.K. removed REMS-type restrictions. These studies show that receiving abortion care through usual pharmacy channels and through telemedicine is safe, effective, and reduces barriers to care.”

Dr. Norman reported receiving grants from the Canadian Institutes of Health Research, providing expert witness services to the government of Ontario and Office of the Attorney General, and serving on the board of directors of the Society of Family Planning. No other researchers reported conflicts of interest. Dr. Espey reported no conflicts of interest. The Canadian Institutes of Health Research and the Women’s Health Research Institute with the support of ICES (formerly known as the Institute for Clinical Evaluative Sciences).

Abortion rates remained stable and adverse events were rare after removal of mifepristone prescribing restrictions in Canada, a new study shows.

“Our study is a signal to other countries that restrictions are not necessary to ensure patient safety,” senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a press release.

“This is the strongest evidence yet that it is safe to provide the abortion pill like most other prescriptions – meaning any doctor or nurse practitioner can prescribe, any pharmacist can dispense, and patients can take the pills if, when, and where they choose,” said lead author Laura Schummers, ScD, a postdoctoral fellow in the same department.

The findings “add to the accumulating evidence that removing restrictions from medication abortion is safe, effective, and improves access,” agreed Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, who was not part of the research team. “This is additional confirmation that it is safe for patients to receive abortion care medications in the ‘normal’ fashion, through a prescription available at a pharmacy,” she said in an interview.

The study, published in the New England Journal of Medicine, compared medical abortion use, safety, and effectiveness in the province of Ontario before the Canadian availability of mifepristone and after it became available without restrictions that are similar to the Risk Evaluation and Mitigation Strategy (REMS) restrictions in place for mifepristone in the United States.

Using linked administrative health data, the researchers created a population-based cohort of all Ontario residents aged 12-49 years who had received abortion services during the study period. In total, 195,183 abortions were performed in the period before mifepristone was approved (January 2012–December 2016), and 84,032 were performed after it was made available without restrictions (Nov. 7, 2017, through March 15, 2020). The vast majority of these abortions (89.3%) were surgical, with about 10% being medically induced, the authors reported.

The study found that, while the overall abortion rate declined over the study period (from 11.9 to 11.3 per 1,000 female residents), the proportion of medical abortions jumped sharply from 2.2% to 31.4%, and the rate of second-trimester abortions declined from 5.5% of all abortions to 5.1%.

Abortion safety outcomes within 6 weeks of abortion remained stable over the two study periods. This included severe adverse events (0.03% vs. 0.04%) such as blood transfusions, abdominal surgery, admission to an ICU, or sepsis during an abortion-related hospitalization; and complications (0.74% vs. 0.69%,) such as genital tract or pelvic infection, hemorrhage, embolism, shock, renal failure, damage to pelvic organs or tissues, and venous complications among other things.

There were slight declines in overall abortion effectiveness, but ongoing pregnancy rates “remained infrequent,” the authors noted. While there was a modest rise in the rates of subsequent uterine evacuation (from 1.0% to 2.2%), and ongoing intrauterine pregnancy continuing until delivery (from 0.03% to 0.08%), the rate of ectopic pregnancy diagnosed within 6 weeks after the abortion date remained stable (from 0.15% to 0.22%).

Canada was the first country in the world to remove all supplemental restrictions on the dispensing and administration of mifepristone, according to the press release. And while professional organizations have called for the removal of such restrictions “because they impede access to abortion services without improving safety,” high-quality data on this are lacking, they added.

The study’s finding are consistent with existing U.S. and U.K. data showing Food and Drug Administration REMS restrictions requiring abortion care medications to be dispensed in a clinic by a certified provider “are unnecessary and create obstacles to early abortion access,” said Dr. Espey. “For clinicians and patients in the U.S., it’s important to note that the increasing number of legislative restrictions on abortion, including medication abortion, are non–evidence based. Politically motivated false claims of safety concerns are countered by this study and others conducted during the pandemic when both the U.S. and U.K. removed REMS-type restrictions. These studies show that receiving abortion care through usual pharmacy channels and through telemedicine is safe, effective, and reduces barriers to care.”

Dr. Norman reported receiving grants from the Canadian Institutes of Health Research, providing expert witness services to the government of Ontario and Office of the Attorney General, and serving on the board of directors of the Society of Family Planning. No other researchers reported conflicts of interest. Dr. Espey reported no conflicts of interest. The Canadian Institutes of Health Research and the Women’s Health Research Institute with the support of ICES (formerly known as the Institute for Clinical Evaluative Sciences).

Abortion rates remained stable and adverse events were rare after removal of mifepristone prescribing restrictions in Canada, a new study shows.

“Our study is a signal to other countries that restrictions are not necessary to ensure patient safety,” senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a press release.

“This is the strongest evidence yet that it is safe to provide the abortion pill like most other prescriptions – meaning any doctor or nurse practitioner can prescribe, any pharmacist can dispense, and patients can take the pills if, when, and where they choose,” said lead author Laura Schummers, ScD, a postdoctoral fellow in the same department.

The findings “add to the accumulating evidence that removing restrictions from medication abortion is safe, effective, and improves access,” agreed Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, who was not part of the research team. “This is additional confirmation that it is safe for patients to receive abortion care medications in the ‘normal’ fashion, through a prescription available at a pharmacy,” she said in an interview.

The study, published in the New England Journal of Medicine, compared medical abortion use, safety, and effectiveness in the province of Ontario before the Canadian availability of mifepristone and after it became available without restrictions that are similar to the Risk Evaluation and Mitigation Strategy (REMS) restrictions in place for mifepristone in the United States.

Using linked administrative health data, the researchers created a population-based cohort of all Ontario residents aged 12-49 years who had received abortion services during the study period. In total, 195,183 abortions were performed in the period before mifepristone was approved (January 2012–December 2016), and 84,032 were performed after it was made available without restrictions (Nov. 7, 2017, through March 15, 2020). The vast majority of these abortions (89.3%) were surgical, with about 10% being medically induced, the authors reported.

The study found that, while the overall abortion rate declined over the study period (from 11.9 to 11.3 per 1,000 female residents), the proportion of medical abortions jumped sharply from 2.2% to 31.4%, and the rate of second-trimester abortions declined from 5.5% of all abortions to 5.1%.

Abortion safety outcomes within 6 weeks of abortion remained stable over the two study periods. This included severe adverse events (0.03% vs. 0.04%) such as blood transfusions, abdominal surgery, admission to an ICU, or sepsis during an abortion-related hospitalization; and complications (0.74% vs. 0.69%,) such as genital tract or pelvic infection, hemorrhage, embolism, shock, renal failure, damage to pelvic organs or tissues, and venous complications among other things.

There were slight declines in overall abortion effectiveness, but ongoing pregnancy rates “remained infrequent,” the authors noted. While there was a modest rise in the rates of subsequent uterine evacuation (from 1.0% to 2.2%), and ongoing intrauterine pregnancy continuing until delivery (from 0.03% to 0.08%), the rate of ectopic pregnancy diagnosed within 6 weeks after the abortion date remained stable (from 0.15% to 0.22%).

Canada was the first country in the world to remove all supplemental restrictions on the dispensing and administration of mifepristone, according to the press release. And while professional organizations have called for the removal of such restrictions “because they impede access to abortion services without improving safety,” high-quality data on this are lacking, they added.

The study’s finding are consistent with existing U.S. and U.K. data showing Food and Drug Administration REMS restrictions requiring abortion care medications to be dispensed in a clinic by a certified provider “are unnecessary and create obstacles to early abortion access,” said Dr. Espey. “For clinicians and patients in the U.S., it’s important to note that the increasing number of legislative restrictions on abortion, including medication abortion, are non–evidence based. Politically motivated false claims of safety concerns are countered by this study and others conducted during the pandemic when both the U.S. and U.K. removed REMS-type restrictions. These studies show that receiving abortion care through usual pharmacy channels and through telemedicine is safe, effective, and reduces barriers to care.”

Dr. Norman reported receiving grants from the Canadian Institutes of Health Research, providing expert witness services to the government of Ontario and Office of the Attorney General, and serving on the board of directors of the Society of Family Planning. No other researchers reported conflicts of interest. Dr. Espey reported no conflicts of interest. The Canadian Institutes of Health Research and the Women’s Health Research Institute with the support of ICES (formerly known as the Institute for Clinical Evaluative Sciences).