Kate Johnson

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.

[email protected]

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.

[email protected]

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.

[email protected]

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).

Pregnant women who were at or above the advanced maternal age (AMA) cutoff of 35 years on their due date received significantly more prenatal care, resulting in a slight decline in perinatal mortality, compared with women who were just a few months younger, according to a new study published in JAMA Health Forum. The findings “suggest that clinicians use the cutoff as a heuristic in their clinical recommendations and service provision,” noted lead author Caroline K. Geiger, PhD, who was a PhD student at Harvard University in Cambridge, Mass., during the course of the study, and now works as an associate health economist at Genentech in San Francisco. She and her coauthors suggest a slightly younger AMA cutoff might be beneficial. “Our results suggest that 3.9 perinatal deaths per 1,000 deliveries in this age range could be averted if patients just a few months younger than the AMA cutoff received similar care to those older than the cutoff,” they wrote. “Although the risk of adverse outcomes increases with maternal age, individuals 4 months older or younger than 35 years should not have different underlying risks.”

The cross-sectional study used a national sample of 51,290 commercially insured individuals who were pregnant between 2008 and 2019 and had delivery dates within 120 days of their 35th birthday. Just over half (50.9%) of the individuals were aged 34.7-34.9 years on their expected delivery date – just below the AMA cutoff – while 49.1% were just over the cutoff at age 35.0-35.3 years. A total of 4.7% had multiple gestation, 4.8% had pregestational diabetes, 4.4% had chronic hypertension, and 9.7% had obesity. There was also a subgroup analysis among individuals with low-risk pregnancy (defined as singleton, with no pregestational diabetes, chronic hypertension, or obesity) because they were less likely to have indications for additional prenatal care.

Although there was a slight, nonstatistically significant increase in the overall number of ob.gyn. visits at the AMA cutoff, compared with below it, the percentage of individuals with any maternal-fetal medicine visit increased by 4.27 percentage points (P < .001) at the cutoff. Additionally, while there was a “modest” increase in total ultrasounds (P = .006), there was a significant increase in detailed ultrasounds (P < .001) at the cutoff, and a “substantial” increase in antepartum surveillance (P < .001), the authors reported.

The AMA designation was associated with a 0.39 percentage-point decline in perinatal mortality (P = .04), “however, there were no significant changes in the proportion of individuals with severe maternal morbidity or with preterm birth or low birth weight at age 35 years,” they wrote.

In the subgroup analysis of low-risk pregnancies, “prenatal care services increased substantially at the 35-year cutoff, and in all cases, the increases at age 35 years for this group were larger than for the full sample,” they noted, adding that there was also a “substantially larger” decline in perinatal mortality at the AMA cutoff (P = .002), compared with the full sample.

The authors noted the need for more rigorous evidence on the value and effect of prenatal care guidelines on pregnancy outcomes. “Although pregnancy-related risks increase with maternal age, there is no known abrupt biological increase in underlying risk precisely at age 35 years,” they wrote, adding that “much of the content of prenatal care guidelines has persisted for decades without strong causal evidence to demonstrate its value.”

Their words echo those of Alex F. Peahl, MD, an ob.gyn. and assistant professor at the Institute for Healthcare Policy and Innovation, at the University of Michigan, in Ann Arbor, MI. In a recent review, Dr. Peahl and her colleague Joel D. Howell, MD, PhD, from the same university (Am J Obstet Gynecol. 2021 Apr;224[4]:339-47), note that the COVID-19 pandemic forced a much-needed rethink of prenatal care and its delivery. A look through the history of prenatal care shows “we have treated visit frequency and modality as fixed boxes, into which we must fit an ever-changing set of care recommendations,” they wrote. “We do not have data to support a specific prenatal visit schedule, recommended number of telemedicine visits, or specifications of additional services, and we never have. However, one thing is clear: we are long overdue for new prenatal care delivery guidelines in the United States.”

But when reached for comment on the new study Dr. Peahl cautioned that its conclusions are “limited and warrant future investigation. … While increased prenatal services may explain the improvement in outcomes, several other explanations should be considered,” she told this publication. “Perhaps, maternity care professional behavior differs for patients who are over the age of 35, resulting in increased caution in interpreting test results and symptoms; perhaps patients are more routinely induced at 39 weeks, limiting stillbirth rate; or perhaps patients are more hypervigilant when given the diagnosis of AMA.”

Priya Rajan, MD, agreed that while the paper showed an association between intensified antenatal interventions and decreased perinatal mortality, it did not show a causal relationship. “The study did not include information on other important factors that are also associated with perinatal risk,” noted Dr. Rajan, who is an associate professor in the department of ob.gyn. at Northwestern University in Chicago. Yet, she acknowledged that the findings “support what many clinicians know, which is that age 35 isn’t some tipping point; rather, obstetric risk is influenced by a range of factors, of which age may be one. This study, particularly when considered in the context of other studies and articles we have seen recently, confirms the need for us to rethink how we care for people during pregnancy and post partum. This includes delving further into understanding what aspects of the prenatal care that we provide have the biggest impact for both maternal and perinatal adverse outcomes.”

The study was supported by grant DGE1745303 from the National Science Foundation Graduate Research Fellowship Program. Dr. Geiger reported being a PhD student during the conduction of the study, but had no other disclosures. Dr. Peahl will soon be a consultant for Maven Clinic. Dr. Rajan had no relevant disclosures.

Pregnant women who were at or above the advanced maternal age (AMA) cutoff of 35 years on their due date received significantly more prenatal care, resulting in a slight decline in perinatal mortality, compared with women who were just a few months younger, according to a new study published in JAMA Health Forum. The findings “suggest that clinicians use the cutoff as a heuristic in their clinical recommendations and service provision,” noted lead author Caroline K. Geiger, PhD, who was a PhD student at Harvard University in Cambridge, Mass., during the course of the study, and now works as an associate health economist at Genentech in San Francisco. She and her coauthors suggest a slightly younger AMA cutoff might be beneficial. “Our results suggest that 3.9 perinatal deaths per 1,000 deliveries in this age range could be averted if patients just a few months younger than the AMA cutoff received similar care to those older than the cutoff,” they wrote. “Although the risk of adverse outcomes increases with maternal age, individuals 4 months older or younger than 35 years should not have different underlying risks.”

The cross-sectional study used a national sample of 51,290 commercially insured individuals who were pregnant between 2008 and 2019 and had delivery dates within 120 days of their 35th birthday. Just over half (50.9%) of the individuals were aged 34.7-34.9 years on their expected delivery date – just below the AMA cutoff – while 49.1% were just over the cutoff at age 35.0-35.3 years. A total of 4.7% had multiple gestation, 4.8% had pregestational diabetes, 4.4% had chronic hypertension, and 9.7% had obesity. There was also a subgroup analysis among individuals with low-risk pregnancy (defined as singleton, with no pregestational diabetes, chronic hypertension, or obesity) because they were less likely to have indications for additional prenatal care.

Although there was a slight, nonstatistically significant increase in the overall number of ob.gyn. visits at the AMA cutoff, compared with below it, the percentage of individuals with any maternal-fetal medicine visit increased by 4.27 percentage points (P < .001) at the cutoff. Additionally, while there was a “modest” increase in total ultrasounds (P = .006), there was a significant increase in detailed ultrasounds (P < .001) at the cutoff, and a “substantial” increase in antepartum surveillance (P < .001), the authors reported.

The AMA designation was associated with a 0.39 percentage-point decline in perinatal mortality (P = .04), “however, there were no significant changes in the proportion of individuals with severe maternal morbidity or with preterm birth or low birth weight at age 35 years,” they wrote.

In the subgroup analysis of low-risk pregnancies, “prenatal care services increased substantially at the 35-year cutoff, and in all cases, the increases at age 35 years for this group were larger than for the full sample,” they noted, adding that there was also a “substantially larger” decline in perinatal mortality at the AMA cutoff (P = .002), compared with the full sample.

The authors noted the need for more rigorous evidence on the value and effect of prenatal care guidelines on pregnancy outcomes. “Although pregnancy-related risks increase with maternal age, there is no known abrupt biological increase in underlying risk precisely at age 35 years,” they wrote, adding that “much of the content of prenatal care guidelines has persisted for decades without strong causal evidence to demonstrate its value.”

Their words echo those of Alex F. Peahl, MD, an ob.gyn. and assistant professor at the Institute for Healthcare Policy and Innovation, at the University of Michigan, in Ann Arbor, MI. In a recent review, Dr. Peahl and her colleague Joel D. Howell, MD, PhD, from the same university (Am J Obstet Gynecol. 2021 Apr;224[4]:339-47), note that the COVID-19 pandemic forced a much-needed rethink of prenatal care and its delivery. A look through the history of prenatal care shows “we have treated visit frequency and modality as fixed boxes, into which we must fit an ever-changing set of care recommendations,” they wrote. “We do not have data to support a specific prenatal visit schedule, recommended number of telemedicine visits, or specifications of additional services, and we never have. However, one thing is clear: we are long overdue for new prenatal care delivery guidelines in the United States.”

But when reached for comment on the new study Dr. Peahl cautioned that its conclusions are “limited and warrant future investigation. … While increased prenatal services may explain the improvement in outcomes, several other explanations should be considered,” she told this publication. “Perhaps, maternity care professional behavior differs for patients who are over the age of 35, resulting in increased caution in interpreting test results and symptoms; perhaps patients are more routinely induced at 39 weeks, limiting stillbirth rate; or perhaps patients are more hypervigilant when given the diagnosis of AMA.”

Priya Rajan, MD, agreed that while the paper showed an association between intensified antenatal interventions and decreased perinatal mortality, it did not show a causal relationship. “The study did not include information on other important factors that are also associated with perinatal risk,” noted Dr. Rajan, who is an associate professor in the department of ob.gyn. at Northwestern University in Chicago. Yet, she acknowledged that the findings “support what many clinicians know, which is that age 35 isn’t some tipping point; rather, obstetric risk is influenced by a range of factors, of which age may be one. This study, particularly when considered in the context of other studies and articles we have seen recently, confirms the need for us to rethink how we care for people during pregnancy and post partum. This includes delving further into understanding what aspects of the prenatal care that we provide have the biggest impact for both maternal and perinatal adverse outcomes.”

The study was supported by grant DGE1745303 from the National Science Foundation Graduate Research Fellowship Program. Dr. Geiger reported being a PhD student during the conduction of the study, but had no other disclosures. Dr. Peahl will soon be a consultant for Maven Clinic. Dr. Rajan had no relevant disclosures.

Pregnant women who were at or above the advanced maternal age (AMA) cutoff of 35 years on their due date received significantly more prenatal care, resulting in a slight decline in perinatal mortality, compared with women who were just a few months younger, according to a new study published in JAMA Health Forum. The findings “suggest that clinicians use the cutoff as a heuristic in their clinical recommendations and service provision,” noted lead author Caroline K. Geiger, PhD, who was a PhD student at Harvard University in Cambridge, Mass., during the course of the study, and now works as an associate health economist at Genentech in San Francisco. She and her coauthors suggest a slightly younger AMA cutoff might be beneficial. “Our results suggest that 3.9 perinatal deaths per 1,000 deliveries in this age range could be averted if patients just a few months younger than the AMA cutoff received similar care to those older than the cutoff,” they wrote. “Although the risk of adverse outcomes increases with maternal age, individuals 4 months older or younger than 35 years should not have different underlying risks.”

The cross-sectional study used a national sample of 51,290 commercially insured individuals who were pregnant between 2008 and 2019 and had delivery dates within 120 days of their 35th birthday. Just over half (50.9%) of the individuals were aged 34.7-34.9 years on their expected delivery date – just below the AMA cutoff – while 49.1% were just over the cutoff at age 35.0-35.3 years. A total of 4.7% had multiple gestation, 4.8% had pregestational diabetes, 4.4% had chronic hypertension, and 9.7% had obesity. There was also a subgroup analysis among individuals with low-risk pregnancy (defined as singleton, with no pregestational diabetes, chronic hypertension, or obesity) because they were less likely to have indications for additional prenatal care.

Although there was a slight, nonstatistically significant increase in the overall number of ob.gyn. visits at the AMA cutoff, compared with below it, the percentage of individuals with any maternal-fetal medicine visit increased by 4.27 percentage points (P < .001) at the cutoff. Additionally, while there was a “modest” increase in total ultrasounds (P = .006), there was a significant increase in detailed ultrasounds (P < .001) at the cutoff, and a “substantial” increase in antepartum surveillance (P < .001), the authors reported.

The AMA designation was associated with a 0.39 percentage-point decline in perinatal mortality (P = .04), “however, there were no significant changes in the proportion of individuals with severe maternal morbidity or with preterm birth or low birth weight at age 35 years,” they wrote.

In the subgroup analysis of low-risk pregnancies, “prenatal care services increased substantially at the 35-year cutoff, and in all cases, the increases at age 35 years for this group were larger than for the full sample,” they noted, adding that there was also a “substantially larger” decline in perinatal mortality at the AMA cutoff (P = .002), compared with the full sample.

The authors noted the need for more rigorous evidence on the value and effect of prenatal care guidelines on pregnancy outcomes. “Although pregnancy-related risks increase with maternal age, there is no known abrupt biological increase in underlying risk precisely at age 35 years,” they wrote, adding that “much of the content of prenatal care guidelines has persisted for decades without strong causal evidence to demonstrate its value.”

Their words echo those of Alex F. Peahl, MD, an ob.gyn. and assistant professor at the Institute for Healthcare Policy and Innovation, at the University of Michigan, in Ann Arbor, MI. In a recent review, Dr. Peahl and her colleague Joel D. Howell, MD, PhD, from the same university (Am J Obstet Gynecol. 2021 Apr;224[4]:339-47), note that the COVID-19 pandemic forced a much-needed rethink of prenatal care and its delivery. A look through the history of prenatal care shows “we have treated visit frequency and modality as fixed boxes, into which we must fit an ever-changing set of care recommendations,” they wrote. “We do not have data to support a specific prenatal visit schedule, recommended number of telemedicine visits, or specifications of additional services, and we never have. However, one thing is clear: we are long overdue for new prenatal care delivery guidelines in the United States.”

But when reached for comment on the new study Dr. Peahl cautioned that its conclusions are “limited and warrant future investigation. … While increased prenatal services may explain the improvement in outcomes, several other explanations should be considered,” she told this publication. “Perhaps, maternity care professional behavior differs for patients who are over the age of 35, resulting in increased caution in interpreting test results and symptoms; perhaps patients are more routinely induced at 39 weeks, limiting stillbirth rate; or perhaps patients are more hypervigilant when given the diagnosis of AMA.”

Priya Rajan, MD, agreed that while the paper showed an association between intensified antenatal interventions and decreased perinatal mortality, it did not show a causal relationship. “The study did not include information on other important factors that are also associated with perinatal risk,” noted Dr. Rajan, who is an associate professor in the department of ob.gyn. at Northwestern University in Chicago. Yet, she acknowledged that the findings “support what many clinicians know, which is that age 35 isn’t some tipping point; rather, obstetric risk is influenced by a range of factors, of which age may be one. This study, particularly when considered in the context of other studies and articles we have seen recently, confirms the need for us to rethink how we care for people during pregnancy and post partum. This includes delving further into understanding what aspects of the prenatal care that we provide have the biggest impact for both maternal and perinatal adverse outcomes.”

The study was supported by grant DGE1745303 from the National Science Foundation Graduate Research Fellowship Program. Dr. Geiger reported being a PhD student during the conduction of the study, but had no other disclosures. Dr. Peahl will soon be a consultant for Maven Clinic. Dr. Rajan had no relevant disclosures.

American teenagers receive less formal sex education today than they did 25 years ago, with “troubling” racial inequities that leave youth of color and queer youth at greater risk than other teens for sexually transmitted diseases and unintended pregnancy, according to a new study.

“Many adolescents do not receive any instruction on essential topics or do not receive this instruction until after the first sex,” wrote Laura D. Lindberg, PhD, and Leslie M. Kantor, PhD, MPH, from the Guttmacher Institute, New York, and the department of urban-global public health at Rutgers University, Piscataway, N.J., respectively. “These gaps in sex education in the U.S. are uneven, and gender, racial, and other disparities are widespread,” they added, calling for “robust efforts ... to ensure equity and reduce health disparities.”

The study used cross-sectional data from the 2011-2015 and 2015-2019 National Surveys of Family Growth (NSFG) to examine content, timing, and location of formal sex education among 15- to 19-year-olds in the United States. The data came from samples of 2,047 females and 2,087 males in 2011-2015, and 1,894 females and 1,918 males in 2015-2019. The majority of respondents were aged 15-17 years and non-Hispanic White, with another quarter being Hispanic, and 14% Black.

The survey asked respondents whether, before they turned 18, they had ever received formal instruction at school, church, a community center, “or some other place” about how to say no to sex, methods of birth control, STDs, how to prevent HIV/AIDS, abstaining until marriage to have sex, where to get birth control, and how to use a condom.

Follow-up questions asked about what grade instruction was first received and whether it had occurred before first penile-vaginal intercourse. The 2015-2019 survey also asked about the location of instruction, but only concerning methods of birth control and abstinence until marriage.

The results showed that HIV and STD prevention was the most commonly reported area of instruction, received by more than 90% of both males and females. However, beyond this there were imbalances, with only about half (49%-55%) of respondents receiving instruction meeting the Surgeon General’s Healthy People 2030 composite sex education goal. Lack of instruction on birth control drove this result for 80% of respondents. Specifically, there was a strong slant emphasizing abstinence over birth control instruction. Over both survey periods and both genders, more respondents reported instruction on how to say no to sex (79%-84%) and abstaining until marriage (58%-73%), compared with where to obtain birth control (40%-53%) or how to use a condom (54%-60%). “Overall, about 20% of adolescents received instruction from multiple sources about waiting until marriage, but only 5%-8% received birth control information from multiple settings,” they reported.

There were racial/ethnic and sexual orientation differences in the scope and balance of instruction reported by teens. Less than half of Black (45%) and Hispanic (47%) males received instruction on the combined Healthy People topics, compared with 57% of White males. Black females were less likely (30%) than White females (45%) to receive information on where to get birth control before the first sex. Nonstraight males were less likely than straight males to receive instruction about STIs or HIV/AIDS (83% vs. 93%).

In addition, religious attendance emerged as a key factor in the receipt of sex education, “with more frequent religious attendance associated with a greater likelihood of instruction about delaying sex and less likelihood of instruction about contraception,” the authors noted.

Comparing their findings to previous NSFG surveys, the researchers commented that “the share of adolescents receiving instruction about birth control was higher in 1995 than in 2015-2019 for both the genders; in 1995, 87% of females and 81% of males reported sex education about birth control methods, compared with 64% and 63% in 2015-2019, respectively.” The findings “should spur policy makers at the national, state, and local levels to ensure the broader provision of sex education and that school districts serving young people of color are the focus of additional efforts and funding.”

Asked for comment, John Santelli, MD, MPH, professor of population and family health and pediatrics at Columbia University, New York, who was not involved with the study, said the findings fit into a series of studies by Lindberg going back to 1988 showing that receipt of formal sex education before age 18 has declined over time.

“We, the adults, in America can do better by our young people,” he said in an interview. “Adolescents need sex education that is science based, medically accurate, and developmentally appropriate. Many adolescents are not receiving education that the CDC and health professionals recommend including information about where to get birth control, condom skills, and even, how to say no to sex. The neglect of young Black and Hispanic men is very concerning. However, we are not doing a great job in educating most of our adolescents. Health care providers can be influential in speaking with parents about their children’s education about sex. We need to activate parents, health care providers, and members of the faith community to investigate what is happening about sex education in their own communities.”

Dr. Santelli noted that there are multiple ways to strengthen the provision of sex education in the United States. In a recent commentary, he and his coauthors highlighted the National Sex Education Standards (NSES), which, “developed in partnership between sex education organizations and health professionals, provide clear, consistent, and straightforward guidance on the essential content for students in grades K-12.” The NSES were also used in the development of the CDC’s recently released Health Education Curriculum Analysis Tool.

The commentary takes a strong stand against the recently released revised Medical Institute for Sexual Heath K-12 Standards for Optimal Sexual Development, which, compared with the NSES, are “seriously flawed from both scientific and human rights’ perspectives,” they wrote. “States and local communities aiming to improve adolescent sexual and reproductive health and looking for national standards on sex education should adopt the NSES.”

Dr. Lindberg and Dr. Kantor disclosed no conflicts of interest. Dr. Santelli teaches public health students about adolescent health and chairs the board of directors of the Sexuality Information and Education Council of the United States. He disclosed no financial conflicts.

American teenagers receive less formal sex education today than they did 25 years ago, with “troubling” racial inequities that leave youth of color and queer youth at greater risk than other teens for sexually transmitted diseases and unintended pregnancy, according to a new study.

“Many adolescents do not receive any instruction on essential topics or do not receive this instruction until after the first sex,” wrote Laura D. Lindberg, PhD, and Leslie M. Kantor, PhD, MPH, from the Guttmacher Institute, New York, and the department of urban-global public health at Rutgers University, Piscataway, N.J., respectively. “These gaps in sex education in the U.S. are uneven, and gender, racial, and other disparities are widespread,” they added, calling for “robust efforts ... to ensure equity and reduce health disparities.”

The study used cross-sectional data from the 2011-2015 and 2015-2019 National Surveys of Family Growth (NSFG) to examine content, timing, and location of formal sex education among 15- to 19-year-olds in the United States. The data came from samples of 2,047 females and 2,087 males in 2011-2015, and 1,894 females and 1,918 males in 2015-2019. The majority of respondents were aged 15-17 years and non-Hispanic White, with another quarter being Hispanic, and 14% Black.

The survey asked respondents whether, before they turned 18, they had ever received formal instruction at school, church, a community center, “or some other place” about how to say no to sex, methods of birth control, STDs, how to prevent HIV/AIDS, abstaining until marriage to have sex, where to get birth control, and how to use a condom.

Follow-up questions asked about what grade instruction was first received and whether it had occurred before first penile-vaginal intercourse. The 2015-2019 survey also asked about the location of instruction, but only concerning methods of birth control and abstinence until marriage.

The results showed that HIV and STD prevention was the most commonly reported area of instruction, received by more than 90% of both males and females. However, beyond this there were imbalances, with only about half (49%-55%) of respondents receiving instruction meeting the Surgeon General’s Healthy People 2030 composite sex education goal. Lack of instruction on birth control drove this result for 80% of respondents. Specifically, there was a strong slant emphasizing abstinence over birth control instruction. Over both survey periods and both genders, more respondents reported instruction on how to say no to sex (79%-84%) and abstaining until marriage (58%-73%), compared with where to obtain birth control (40%-53%) or how to use a condom (54%-60%). “Overall, about 20% of adolescents received instruction from multiple sources about waiting until marriage, but only 5%-8% received birth control information from multiple settings,” they reported.

There were racial/ethnic and sexual orientation differences in the scope and balance of instruction reported by teens. Less than half of Black (45%) and Hispanic (47%) males received instruction on the combined Healthy People topics, compared with 57% of White males. Black females were less likely (30%) than White females (45%) to receive information on where to get birth control before the first sex. Nonstraight males were less likely than straight males to receive instruction about STIs or HIV/AIDS (83% vs. 93%).

In addition, religious attendance emerged as a key factor in the receipt of sex education, “with more frequent religious attendance associated with a greater likelihood of instruction about delaying sex and less likelihood of instruction about contraception,” the authors noted.

Comparing their findings to previous NSFG surveys, the researchers commented that “the share of adolescents receiving instruction about birth control was higher in 1995 than in 2015-2019 for both the genders; in 1995, 87% of females and 81% of males reported sex education about birth control methods, compared with 64% and 63% in 2015-2019, respectively.” The findings “should spur policy makers at the national, state, and local levels to ensure the broader provision of sex education and that school districts serving young people of color are the focus of additional efforts and funding.”

Asked for comment, John Santelli, MD, MPH, professor of population and family health and pediatrics at Columbia University, New York, who was not involved with the study, said the findings fit into a series of studies by Lindberg going back to 1988 showing that receipt of formal sex education before age 18 has declined over time.

“We, the adults, in America can do better by our young people,” he said in an interview. “Adolescents need sex education that is science based, medically accurate, and developmentally appropriate. Many adolescents are not receiving education that the CDC and health professionals recommend including information about where to get birth control, condom skills, and even, how to say no to sex. The neglect of young Black and Hispanic men is very concerning. However, we are not doing a great job in educating most of our adolescents. Health care providers can be influential in speaking with parents about their children’s education about sex. We need to activate parents, health care providers, and members of the faith community to investigate what is happening about sex education in their own communities.”

Dr. Santelli noted that there are multiple ways to strengthen the provision of sex education in the United States. In a recent commentary, he and his coauthors highlighted the National Sex Education Standards (NSES), which, “developed in partnership between sex education organizations and health professionals, provide clear, consistent, and straightforward guidance on the essential content for students in grades K-12.” The NSES were also used in the development of the CDC’s recently released Health Education Curriculum Analysis Tool.

The commentary takes a strong stand against the recently released revised Medical Institute for Sexual Heath K-12 Standards for Optimal Sexual Development, which, compared with the NSES, are “seriously flawed from both scientific and human rights’ perspectives,” they wrote. “States and local communities aiming to improve adolescent sexual and reproductive health and looking for national standards on sex education should adopt the NSES.”

Dr. Lindberg and Dr. Kantor disclosed no conflicts of interest. Dr. Santelli teaches public health students about adolescent health and chairs the board of directors of the Sexuality Information and Education Council of the United States. He disclosed no financial conflicts.

American teenagers receive less formal sex education today than they did 25 years ago, with “troubling” racial inequities that leave youth of color and queer youth at greater risk than other teens for sexually transmitted diseases and unintended pregnancy, according to a new study.

“Many adolescents do not receive any instruction on essential topics or do not receive this instruction until after the first sex,” wrote Laura D. Lindberg, PhD, and Leslie M. Kantor, PhD, MPH, from the Guttmacher Institute, New York, and the department of urban-global public health at Rutgers University, Piscataway, N.J., respectively. “These gaps in sex education in the U.S. are uneven, and gender, racial, and other disparities are widespread,” they added, calling for “robust efforts ... to ensure equity and reduce health disparities.”

The study used cross-sectional data from the 2011-2015 and 2015-2019 National Surveys of Family Growth (NSFG) to examine content, timing, and location of formal sex education among 15- to 19-year-olds in the United States. The data came from samples of 2,047 females and 2,087 males in 2011-2015, and 1,894 females and 1,918 males in 2015-2019. The majority of respondents were aged 15-17 years and non-Hispanic White, with another quarter being Hispanic, and 14% Black.

The survey asked respondents whether, before they turned 18, they had ever received formal instruction at school, church, a community center, “or some other place” about how to say no to sex, methods of birth control, STDs, how to prevent HIV/AIDS, abstaining until marriage to have sex, where to get birth control, and how to use a condom.

Follow-up questions asked about what grade instruction was first received and whether it had occurred before first penile-vaginal intercourse. The 2015-2019 survey also asked about the location of instruction, but only concerning methods of birth control and abstinence until marriage.

The results showed that HIV and STD prevention was the most commonly reported area of instruction, received by more than 90% of both males and females. However, beyond this there were imbalances, with only about half (49%-55%) of respondents receiving instruction meeting the Surgeon General’s Healthy People 2030 composite sex education goal. Lack of instruction on birth control drove this result for 80% of respondents. Specifically, there was a strong slant emphasizing abstinence over birth control instruction. Over both survey periods and both genders, more respondents reported instruction on how to say no to sex (79%-84%) and abstaining until marriage (58%-73%), compared with where to obtain birth control (40%-53%) or how to use a condom (54%-60%). “Overall, about 20% of adolescents received instruction from multiple sources about waiting until marriage, but only 5%-8% received birth control information from multiple settings,” they reported.

There were racial/ethnic and sexual orientation differences in the scope and balance of instruction reported by teens. Less than half of Black (45%) and Hispanic (47%) males received instruction on the combined Healthy People topics, compared with 57% of White males. Black females were less likely (30%) than White females (45%) to receive information on where to get birth control before the first sex. Nonstraight males were less likely than straight males to receive instruction about STIs or HIV/AIDS (83% vs. 93%).

In addition, religious attendance emerged as a key factor in the receipt of sex education, “with more frequent religious attendance associated with a greater likelihood of instruction about delaying sex and less likelihood of instruction about contraception,” the authors noted.

Comparing their findings to previous NSFG surveys, the researchers commented that “the share of adolescents receiving instruction about birth control was higher in 1995 than in 2015-2019 for both the genders; in 1995, 87% of females and 81% of males reported sex education about birth control methods, compared with 64% and 63% in 2015-2019, respectively.” The findings “should spur policy makers at the national, state, and local levels to ensure the broader provision of sex education and that school districts serving young people of color are the focus of additional efforts and funding.”

Asked for comment, John Santelli, MD, MPH, professor of population and family health and pediatrics at Columbia University, New York, who was not involved with the study, said the findings fit into a series of studies by Lindberg going back to 1988 showing that receipt of formal sex education before age 18 has declined over time.

“We, the adults, in America can do better by our young people,” he said in an interview. “Adolescents need sex education that is science based, medically accurate, and developmentally appropriate. Many adolescents are not receiving education that the CDC and health professionals recommend including information about where to get birth control, condom skills, and even, how to say no to sex. The neglect of young Black and Hispanic men is very concerning. However, we are not doing a great job in educating most of our adolescents. Health care providers can be influential in speaking with parents about their children’s education about sex. We need to activate parents, health care providers, and members of the faith community to investigate what is happening about sex education in their own communities.”

Dr. Santelli noted that there are multiple ways to strengthen the provision of sex education in the United States. In a recent commentary, he and his coauthors highlighted the National Sex Education Standards (NSES), which, “developed in partnership between sex education organizations and health professionals, provide clear, consistent, and straightforward guidance on the essential content for students in grades K-12.” The NSES were also used in the development of the CDC’s recently released Health Education Curriculum Analysis Tool.

The commentary takes a strong stand against the recently released revised Medical Institute for Sexual Heath K-12 Standards for Optimal Sexual Development, which, compared with the NSES, are “seriously flawed from both scientific and human rights’ perspectives,” they wrote. “States and local communities aiming to improve adolescent sexual and reproductive health and looking for national standards on sex education should adopt the NSES.”

Dr. Lindberg and Dr. Kantor disclosed no conflicts of interest. Dr. Santelli teaches public health students about adolescent health and chairs the board of directors of the Sexuality Information and Education Council of the United States. He disclosed no financial conflicts.

The association of atopic dermatitis (AD) with short stature and increased body mass index (BMI) in early childhood may be transient, often resolving by midadolescence, according to a large cohort study published online in JAMA Dermatology.

“The potential for ‘catch up’ in height for children with atopic dermatitis observed in our study may be explained with resolution of atopic dermatitis or successful treatment,” write senior author Aaron M. Drucker, MD, ScM, from the division of dermatology, University of Toronto, and Women’s College Hospital in Toronto, and colleagues. They postulated that, while the association between AD and shorter height is “is likely multifactorial,” it may be driven in part by sleep loss caused by AD, or corticosteroid treatment of AD, both of which can result in growth retardation and subsequent increased BMI.

The researchers used data from TARGet Kids!, a prospective, longitudinal cohort study designed to study multiple health conditions in children from general pediatric and family practices across Toronto. Their study included 10,611 children for whom there was data on height, weight, BMI, and standardized z scores, which account for age and sex differences in anthropometric characteristics. Clinically relevant covariates that were collected included child age, sex, birth weight, history of asthma, family income, maternal and paternal ethnicity, and maternal height and BMI.

The mean age of the children in the study at cohort entry was 23 months, and they were followed for a median of 28.5 months, during which time they had a median of two visits. At baseline, 947 (8.9%) children had parent-reported AD, with this number rising to 1,834 (17.3%) during follow-up.

After adjusting for covariates, AD was associated with lower mean z-height (P < .001), higher mean z-BMI (P = .008), but lower mean z-weight (P < .001), compared with children without AD. Using World Health Organization growth tables, the researchers estimated that “children with atopic dermatitis were, on average, approximately 0.5 cm shorter at age 2 years and 0.6 cm shorter at age 5 years than children without atopic dermatitis” after adjusting for covariates. They also estimated that children with AD were “on average, approximately 0.2 more BMI units at age 2 years” than children without AD. The associations between AD and height diminished by age 14 years, as did the association between AD and BMI by age 5.5 years.

“Given that we found children with atopic dermatitis to be somewhat less heavy, as measured by z-weight, than children without atopic dermatitis and that this association did not attenuate with age, it is possible that our findings for BMI, and perhaps those of previous studies, are explained mainly by differences in height,” the authors write. “This distinction has obvious clinical importance – rather than a focus on obesity and obesogenic behaviors being problematic in children with atopic dermatitis, research might be better directed at understanding the association between atopic dermatitis and initially shorter stature.”

Asked to comment on the study results, Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, told this news organization he would have preferred using the wording “in addition to focusing on obesity,” rather than “focus on obesity.”

“We should not ignore diet and sedentary activity as important factors,” he said, pointing to another recent study that found higher rates of eating disorders associated with AD.

Dr. Silverberg said that he was not familiar enough with the cohort sample to comment on how representative it is of the Canadian population, or on how generalizable the results are to other regions and populations. Generalizability, he added, “is an important issue, as we previously found regional differences with respect to the association between AD and obesity.”

In addition, he noted that in the study AD was defined as an “ever history” of disease rather than “in the past year or currently,” so, even though it is a longitudinal study, “it is really looking at how AD at any point in patients’ lives is related to weight or stature,” he explained. But, he added, “many cases of childhood AD ‘burn out’ or become milder/clear as the children get older. So, if the AD clears, then one would expect to see attenuation of associations as the children get older. However, this doesn’t tell us about how persistent AD into later childhood or adolescence is related to height or weight.”

Previous studies found that short stature and obesity were particularly associated with moderate – and even more to severe – atopic dermatitis, Dr. Silverberg said. It is likely that most patients in this primary care cohort had mild disease, he noted, so the effect sizes are likely diluted by mostly mild disease “and not relevant to the more persistent and severe AD patients encountered in the dermatology practice setting.” 

The study was supported by the department of medicine, Women’s College Hospital, and the Canadian Institutes of Health Research.

One author reported receiving compensation from the British Journal of Dermatology, the American Academy of Dermatology, and the National Eczema Association and has served as a paid consultant for the Canadian Agency for Drugs and Technologies in Health outside the submitted work. No other disclosures were reported. Dr. Silverberg has disclosed no relevant financial relationships.
 

Commentary by Robert Sidbury, MD, MPH

Among the more puzzling “associations” to emerge in recent literature has been the association between atopic dermatitis (AD) and obesity. I see many children with severe AD every day and my gestalt “association” is a thinner, shorter child rather than an overweight one. Dr. Drucker and colleagues’ data has helped me understand this dissonance. Children with AD do in fact, on average, weigh less but they are also shorter, possibly explaining their higher body mass index (BMI). More important, these findings are transient, with height differences dissipating by 14 years of age, and BMI differences by kindergarten. This information should train providers’ sights on optimal AD treatment and optimal nutritional and lifestyle support without undue concern for obesity or obesogenic behaviors.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

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

This article was updated 6/18/22.

The association of atopic dermatitis (AD) with short stature and increased body mass index (BMI) in early childhood may be transient, often resolving by midadolescence, according to a large cohort study published online in JAMA Dermatology.

“The potential for ‘catch up’ in height for children with atopic dermatitis observed in our study may be explained with resolution of atopic dermatitis or successful treatment,” write senior author Aaron M. Drucker, MD, ScM, from the division of dermatology, University of Toronto, and Women’s College Hospital in Toronto, and colleagues. They postulated that, while the association between AD and shorter height is “is likely multifactorial,” it may be driven in part by sleep loss caused by AD, or corticosteroid treatment of AD, both of which can result in growth retardation and subsequent increased BMI.

The researchers used data from TARGet Kids!, a prospective, longitudinal cohort study designed to study multiple health conditions in children from general pediatric and family practices across Toronto. Their study included 10,611 children for whom there was data on height, weight, BMI, and standardized z scores, which account for age and sex differences in anthropometric characteristics. Clinically relevant covariates that were collected included child age, sex, birth weight, history of asthma, family income, maternal and paternal ethnicity, and maternal height and BMI.

The mean age of the children in the study at cohort entry was 23 months, and they were followed for a median of 28.5 months, during which time they had a median of two visits. At baseline, 947 (8.9%) children had parent-reported AD, with this number rising to 1,834 (17.3%) during follow-up.

After adjusting for covariates, AD was associated with lower mean z-height (P < .001), higher mean z-BMI (P = .008), but lower mean z-weight (P < .001), compared with children without AD. Using World Health Organization growth tables, the researchers estimated that “children with atopic dermatitis were, on average, approximately 0.5 cm shorter at age 2 years and 0.6 cm shorter at age 5 years than children without atopic dermatitis” after adjusting for covariates. They also estimated that children with AD were “on average, approximately 0.2 more BMI units at age 2 years” than children without AD. The associations between AD and height diminished by age 14 years, as did the association between AD and BMI by age 5.5 years.

“Given that we found children with atopic dermatitis to be somewhat less heavy, as measured by z-weight, than children without atopic dermatitis and that this association did not attenuate with age, it is possible that our findings for BMI, and perhaps those of previous studies, are explained mainly by differences in height,” the authors write. “This distinction has obvious clinical importance – rather than a focus on obesity and obesogenic behaviors being problematic in children with atopic dermatitis, research might be better directed at understanding the association between atopic dermatitis and initially shorter stature.”

Asked to comment on the study results, Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, told this news organization he would have preferred using the wording “in addition to focusing on obesity,” rather than “focus on obesity.”

“We should not ignore diet and sedentary activity as important factors,” he said, pointing to another recent study that found higher rates of eating disorders associated with AD.

Dr. Silverberg said that he was not familiar enough with the cohort sample to comment on how representative it is of the Canadian population, or on how generalizable the results are to other regions and populations. Generalizability, he added, “is an important issue, as we previously found regional differences with respect to the association between AD and obesity.”

In addition, he noted that in the study AD was defined as an “ever history” of disease rather than “in the past year or currently,” so, even though it is a longitudinal study, “it is really looking at how AD at any point in patients’ lives is related to weight or stature,” he explained. But, he added, “many cases of childhood AD ‘burn out’ or become milder/clear as the children get older. So, if the AD clears, then one would expect to see attenuation of associations as the children get older. However, this doesn’t tell us about how persistent AD into later childhood or adolescence is related to height or weight.”

Previous studies found that short stature and obesity were particularly associated with moderate – and even more to severe – atopic dermatitis, Dr. Silverberg said. It is likely that most patients in this primary care cohort had mild disease, he noted, so the effect sizes are likely diluted by mostly mild disease “and not relevant to the more persistent and severe AD patients encountered in the dermatology practice setting.” 

The study was supported by the department of medicine, Women’s College Hospital, and the Canadian Institutes of Health Research.

One author reported receiving compensation from the British Journal of Dermatology, the American Academy of Dermatology, and the National Eczema Association and has served as a paid consultant for the Canadian Agency for Drugs and Technologies in Health outside the submitted work. No other disclosures were reported. Dr. Silverberg has disclosed no relevant financial relationships.
 

Commentary by Robert Sidbury, MD, MPH

Among the more puzzling “associations” to emerge in recent literature has been the association between atopic dermatitis (AD) and obesity. I see many children with severe AD every day and my gestalt “association” is a thinner, shorter child rather than an overweight one. Dr. Drucker and colleagues’ data has helped me understand this dissonance. Children with AD do in fact, on average, weigh less but they are also shorter, possibly explaining their higher body mass index (BMI). More important, these findings are transient, with height differences dissipating by 14 years of age, and BMI differences by kindergarten. This information should train providers’ sights on optimal AD treatment and optimal nutritional and lifestyle support without undue concern for obesity or obesogenic behaviors.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

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

This article was updated 6/18/22.

The association of atopic dermatitis (AD) with short stature and increased body mass index (BMI) in early childhood may be transient, often resolving by midadolescence, according to a large cohort study published online in JAMA Dermatology.

“The potential for ‘catch up’ in height for children with atopic dermatitis observed in our study may be explained with resolution of atopic dermatitis or successful treatment,” write senior author Aaron M. Drucker, MD, ScM, from the division of dermatology, University of Toronto, and Women’s College Hospital in Toronto, and colleagues. They postulated that, while the association between AD and shorter height is “is likely multifactorial,” it may be driven in part by sleep loss caused by AD, or corticosteroid treatment of AD, both of which can result in growth retardation and subsequent increased BMI.

The researchers used data from TARGet Kids!, a prospective, longitudinal cohort study designed to study multiple health conditions in children from general pediatric and family practices across Toronto. Their study included 10,611 children for whom there was data on height, weight, BMI, and standardized z scores, which account for age and sex differences in anthropometric characteristics. Clinically relevant covariates that were collected included child age, sex, birth weight, history of asthma, family income, maternal and paternal ethnicity, and maternal height and BMI.

The mean age of the children in the study at cohort entry was 23 months, and they were followed for a median of 28.5 months, during which time they had a median of two visits. At baseline, 947 (8.9%) children had parent-reported AD, with this number rising to 1,834 (17.3%) during follow-up.

After adjusting for covariates, AD was associated with lower mean z-height (P < .001), higher mean z-BMI (P = .008), but lower mean z-weight (P < .001), compared with children without AD. Using World Health Organization growth tables, the researchers estimated that “children with atopic dermatitis were, on average, approximately 0.5 cm shorter at age 2 years and 0.6 cm shorter at age 5 years than children without atopic dermatitis” after adjusting for covariates. They also estimated that children with AD were “on average, approximately 0.2 more BMI units at age 2 years” than children without AD. The associations between AD and height diminished by age 14 years, as did the association between AD and BMI by age 5.5 years.

“Given that we found children with atopic dermatitis to be somewhat less heavy, as measured by z-weight, than children without atopic dermatitis and that this association did not attenuate with age, it is possible that our findings for BMI, and perhaps those of previous studies, are explained mainly by differences in height,” the authors write. “This distinction has obvious clinical importance – rather than a focus on obesity and obesogenic behaviors being problematic in children with atopic dermatitis, research might be better directed at understanding the association between atopic dermatitis and initially shorter stature.”

Asked to comment on the study results, Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, told this news organization he would have preferred using the wording “in addition to focusing on obesity,” rather than “focus on obesity.”

“We should not ignore diet and sedentary activity as important factors,” he said, pointing to another recent study that found higher rates of eating disorders associated with AD.

Dr. Silverberg said that he was not familiar enough with the cohort sample to comment on how representative it is of the Canadian population, or on how generalizable the results are to other regions and populations. Generalizability, he added, “is an important issue, as we previously found regional differences with respect to the association between AD and obesity.”

In addition, he noted that in the study AD was defined as an “ever history” of disease rather than “in the past year or currently,” so, even though it is a longitudinal study, “it is really looking at how AD at any point in patients’ lives is related to weight or stature,” he explained. But, he added, “many cases of childhood AD ‘burn out’ or become milder/clear as the children get older. So, if the AD clears, then one would expect to see attenuation of associations as the children get older. However, this doesn’t tell us about how persistent AD into later childhood or adolescence is related to height or weight.”

Previous studies found that short stature and obesity were particularly associated with moderate – and even more to severe – atopic dermatitis, Dr. Silverberg said. It is likely that most patients in this primary care cohort had mild disease, he noted, so the effect sizes are likely diluted by mostly mild disease “and not relevant to the more persistent and severe AD patients encountered in the dermatology practice setting.” 

The study was supported by the department of medicine, Women’s College Hospital, and the Canadian Institutes of Health Research.

One author reported receiving compensation from the British Journal of Dermatology, the American Academy of Dermatology, and the National Eczema Association and has served as a paid consultant for the Canadian Agency for Drugs and Technologies in Health outside the submitted work. No other disclosures were reported. Dr. Silverberg has disclosed no relevant financial relationships.
 

Commentary by Robert Sidbury, MD, MPH

Among the more puzzling “associations” to emerge in recent literature has been the association between atopic dermatitis (AD) and obesity. I see many children with severe AD every day and my gestalt “association” is a thinner, shorter child rather than an overweight one. Dr. Drucker and colleagues’ data has helped me understand this dissonance. Children with AD do in fact, on average, weigh less but they are also shorter, possibly explaining their higher body mass index (BMI). More important, these findings are transient, with height differences dissipating by 14 years of age, and BMI differences by kindergarten. This information should train providers’ sights on optimal AD treatment and optimal nutritional and lifestyle support without undue concern for obesity or obesogenic behaviors.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

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

This article was updated 6/18/22.

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

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

This article was updated 6/18/22.