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Misinterpretation is a science, not an art
It isn’t autocorrect’s fault this time, we swear
We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?
Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.
Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.
In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.
That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.
Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
Singing … your … lungs … out
There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.
A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.
After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.
So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
And the word of the year is …
Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.
We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”
Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.
Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!
It isn’t autocorrect’s fault this time, we swear
We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?
Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.
Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.
In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.
That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.
Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
Singing … your … lungs … out
There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.
A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.
After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.
So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
And the word of the year is …
Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.
We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”
Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.
Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!
It isn’t autocorrect’s fault this time, we swear
We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?
Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.
Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.
In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.
That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.
Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
Singing … your … lungs … out
There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.
A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.
After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.
So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
And the word of the year is …
Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.
We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”
Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.
Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!
Poorly controlled asthma predicts COVID-19 hospitalization in children
Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.
Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.
Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.
The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.
Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.
The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).
When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.
These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.
In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.
The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.
The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.
The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.
“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
Findings support value of vaccination for children with asthma
“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.
“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.
Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.
“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.
“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.
Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.
The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.
Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.
Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.
Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.
The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.
Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.
The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).
When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.
These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.
In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.
The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.
The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.
The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.
“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
Findings support value of vaccination for children with asthma
“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.
“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.
Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.
“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.
“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.
Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.
The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.
Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.
Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.
Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.
The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.
Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.
The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).
When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.
These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.
In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.
The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.
The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.
The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.
“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
Findings support value of vaccination for children with asthma
“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.
“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.
Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.
“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.
“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.
Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.
The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.
FROM THE LANCET
‘Top’ surgery for trans youth: Advance or dangerous medicine?
Is the gender-affirmative treatment approach an example of “medicine continuing on its progressive march of improving human life” or “a manifestation of dangerous medicine that ... will cause more harm than benefit to vulnerable youths?” wonders an Australian psychiatrist in a newly published letter that addresses the controversial procedure of masculinizing chest surgery – a double mastectomy – in young people with gender dysphoria (GD).
Alison Clayton, MBBS, explores the evidence for masculinizing chest surgery and looks back at examples of “dangerous medicine” in the past century while looking forward, wondering how future medics will retrospectively view gender affirmative treatment, especially so-called “top” or masculinizing chest surgery, which is in actual fact a double mastectomy, in a letter published Nov. 22 in the Archives of Sexual Behavior.
“It is surprising that clinicians and researchers claim chest surgery for GD youth is an evidence-based intervention, rather than acknowledging it is an experimental treatment that requires more rigorous and human research ethics committee [HREC] approved research,” she writes.
“The medical profession needs to consider whether, in its championing of the gender-affirmative approach for GD youth, it is also acting brashly and making mistakes that will negatively impact some young people for the rest of their lives,” she continues.
Ms. Clayton, after many years of experience as a psychiatrist, has recently returned to postgraduate research into the history of 20th-century psychiatry at the School of Historical and Philosophical Studies, University of Melbourne.
Meanwhile, the authors of a viewpoint published online Dec. 1 in JAMA Surgery, agree with Ms. Clayton on the issue of a lack of long-term studies on which to base decisions, particularly when it comes to insurance coverage for gender surgeries in the United States.
Nnenaya Agochukwu-Mmonu, MD, and colleagues recommend use of the coverage with evidence development (CED) approach, which would, they say, provide a “rigorous evidence base for gender-affirming interventions and surgery while simultaneously allowing access and provisional coverage for these services.”
Threefold increase in gender-affirming surgeries in past decade
There has been a threefold rise in the rate of gender-affirming surgeries in the United States in the past decade, which can be attributed to increased recognition of gender dysphoria, decreasing social stigma toward these individuals, greater clinical experience, and expanding insurance coverage, according to Dr. Agochukwu-Mmonu, of the department of urology, NYU School of Medicine, and coauthors.
Ms. Clayton meanwhile notes that of the increasing number of adolescents being referred for treatment for gender dysphoria in the Western world, most were born female and many have “a history of psychiatric illness or neurodevelopmental disorders.”
Many of these youngsters also show a “high demand” for surgical removal of breasts, she adds, noting that this operation is being undertaken as routine treatment in patients as young as 13, with some clinicians arguing that “this surgery is an evidence-based intervention that improves mental health outcomes, and that it is discriminatory for it not to be available.”
She also notes that “chest dysphoria” is “a recently created term meaning discomfort with one’s breasts.” The term “breast” is therefore largely absent in publications talking about this surgery as it “may cause distress for transgender males,” to quote one source, Ms. Clayton says, and “this seems part of a broader pattern of removing this term from clinical language,” according to another article on the subject.
Ms. Clayton also says, “There are only a handful of published studies focusing on the potential benefits of masculinizing chest surgery,” and notes that these mostly report on surgery for individuals younger than 21 years old.
Significant methodological flaws in existing research
One study of 14 postsurgical youth (nine of whom were under 18 years) found that “all reported high aesthetic satisfaction and most self-reported low complication rates and improvement in mood.”
Another cross-sectional retrospective survey looked at 68 postsurgical transmasculine youth (72% of the eligible postsurgical population); 49% had surgery when younger than age 18, with the youngest being age 13 and the oldest age 24. At the time of the survey, only 14% of participants were more than 2 years postsurgery. The postsurgical participants were found to have reduced chest dysphoria (the outcome) compared with a convenience and nonmatched comparison sample of nonsurgical transmasculine youth.
And a 2021 qualitative study of 30 transmale youth – about half of whom had undergone chest surgery – concluded that the postsurgical cohort experienced “tremendous” benefits in chest dysphoria and a range of psychological outcomes.
On this particular study, Ms. Clayton notes that “in my opinion, they did not provide enough detail for the reader to make an informed judgment regarding this latter claim.”
She goes on to discuss genital surgery, sometimes called full gender-affirming surgery (or “bottom surgery”), and says proponents of these operations point out that the main objections to them in minors is to “surgical sterilization, and people get super worked up about that ... it is a barrier we have to overcome, and I think we are going to.”
Ms. Clayton asserts that it seems “this barrier is already being overcome, as it has been reported that in the United States, genital surgery is being undertaken on gender dysphoric minors as young as 15 years old.”
Reflecting on the available evidence, Ms. Clayton highlights the significant methodological flaws that limit the extent to which surgery can be linked to short-term improved mental health outcomes and adds that information on long-term outcomes and rates of regret is unavailable.
She also asserts that the research fails to assess “a role for psychological interventions which could be utilized, as a least-harm intervention, until maturity is reached.”
Historical examples of experimental medicine
Ms. Clayton goes on to draw parallels with experimental medicine performed on homosexuals in the 20th century, highlighting the medical and surgical interventions, which included metrazol convulsive therapy, chemical castration with estrogens, surgical castration, clitoridectomy, brain operations, and aversive electrotherapy.
She also refers to the historical practice of hormonal treatment for “tall girls” and “short boys” between the 1960s and 1980s. Hormones were given to young people who did not have any medical reason underpinning their stature but were distressed, and society considered their height to have a negative social impact.
“With the encouragement of physicians and school nurses, enthusiastic media promotion, and pharmaceutical companies’ advertising, parents sought hormonal interventions,” she writes, adding that, at the time the hormones were considered safe, but long-term adverse effects emerged, including impaired fertility and increased risk of cancers.
“This seems another part of the story of medicine acting to reinforce society’s sex stereotypes, and for some patients it came at disastrous personal cost,” writes Ms. Clayton.
The gender-affirming approach is based on endorsing the adolescent’s stated gender identity with minimal questioning and “that they should be supported to undertake social transition, medical transition, masculinizing chest surgery, and, some also argue, genital surgery,” she writes.
Objectors to this approach pinpoint the “limited and low-quality evidence base for the benefits” but also “the irreversible and long-term adverse impacts of these treatments on fertility and sexual function, as well as on bone, brain, and cardiovascular functioning.”
Current studies of gender-affirming surgeries lack standardization
In their viewpoint, Dr. Agochukwu-Mmonu and colleagues state that use of a CED would not only help provide an evidence base but would also ensure better-informed policy access and coverage decisions to help standardize approaches to gender surgery in the United States.
Currently, they note, “Studies examining the mental health benefit for patients undergoing gender-affirming surgeries include measures that lack standardization, evaluate different interventions (that is, surgeries are rarely done with concurrent hormone administration), include dissimilar patient populations, and use different study designs.”
This difference in study design leads to variation in reported outcomes. Although many studies have shown benefit, others report that patients have unrealistic expectations or experience regret, Dr. Agochukwu-Mmonu and coauthors conclude.
CED provides an option that would enable informed decisions. “It allows the deliberate use of innovative therapies, explicit integration of transgender and nonbinary patient input, and ongoing systematic evaluation aimed to identify specific patient groups who would or would not benefit from their use.”
This leads back to Ms. Clayton’s central question around whether the gender-affirmative approach is a medical advance or dangerous medicine.
“Why are these experimental interventions, with inherent risks and scarce, low-quality evidence for benefits being implemented outside HREC-regulated clinical trial settings?’” she wonders.
Ms. Clayton has declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
Is the gender-affirmative treatment approach an example of “medicine continuing on its progressive march of improving human life” or “a manifestation of dangerous medicine that ... will cause more harm than benefit to vulnerable youths?” wonders an Australian psychiatrist in a newly published letter that addresses the controversial procedure of masculinizing chest surgery – a double mastectomy – in young people with gender dysphoria (GD).
Alison Clayton, MBBS, explores the evidence for masculinizing chest surgery and looks back at examples of “dangerous medicine” in the past century while looking forward, wondering how future medics will retrospectively view gender affirmative treatment, especially so-called “top” or masculinizing chest surgery, which is in actual fact a double mastectomy, in a letter published Nov. 22 in the Archives of Sexual Behavior.
“It is surprising that clinicians and researchers claim chest surgery for GD youth is an evidence-based intervention, rather than acknowledging it is an experimental treatment that requires more rigorous and human research ethics committee [HREC] approved research,” she writes.
“The medical profession needs to consider whether, in its championing of the gender-affirmative approach for GD youth, it is also acting brashly and making mistakes that will negatively impact some young people for the rest of their lives,” she continues.
Ms. Clayton, after many years of experience as a psychiatrist, has recently returned to postgraduate research into the history of 20th-century psychiatry at the School of Historical and Philosophical Studies, University of Melbourne.
Meanwhile, the authors of a viewpoint published online Dec. 1 in JAMA Surgery, agree with Ms. Clayton on the issue of a lack of long-term studies on which to base decisions, particularly when it comes to insurance coverage for gender surgeries in the United States.
Nnenaya Agochukwu-Mmonu, MD, and colleagues recommend use of the coverage with evidence development (CED) approach, which would, they say, provide a “rigorous evidence base for gender-affirming interventions and surgery while simultaneously allowing access and provisional coverage for these services.”
Threefold increase in gender-affirming surgeries in past decade
There has been a threefold rise in the rate of gender-affirming surgeries in the United States in the past decade, which can be attributed to increased recognition of gender dysphoria, decreasing social stigma toward these individuals, greater clinical experience, and expanding insurance coverage, according to Dr. Agochukwu-Mmonu, of the department of urology, NYU School of Medicine, and coauthors.
Ms. Clayton meanwhile notes that of the increasing number of adolescents being referred for treatment for gender dysphoria in the Western world, most were born female and many have “a history of psychiatric illness or neurodevelopmental disorders.”
Many of these youngsters also show a “high demand” for surgical removal of breasts, she adds, noting that this operation is being undertaken as routine treatment in patients as young as 13, with some clinicians arguing that “this surgery is an evidence-based intervention that improves mental health outcomes, and that it is discriminatory for it not to be available.”
She also notes that “chest dysphoria” is “a recently created term meaning discomfort with one’s breasts.” The term “breast” is therefore largely absent in publications talking about this surgery as it “may cause distress for transgender males,” to quote one source, Ms. Clayton says, and “this seems part of a broader pattern of removing this term from clinical language,” according to another article on the subject.
Ms. Clayton also says, “There are only a handful of published studies focusing on the potential benefits of masculinizing chest surgery,” and notes that these mostly report on surgery for individuals younger than 21 years old.
Significant methodological flaws in existing research
One study of 14 postsurgical youth (nine of whom were under 18 years) found that “all reported high aesthetic satisfaction and most self-reported low complication rates and improvement in mood.”
Another cross-sectional retrospective survey looked at 68 postsurgical transmasculine youth (72% of the eligible postsurgical population); 49% had surgery when younger than age 18, with the youngest being age 13 and the oldest age 24. At the time of the survey, only 14% of participants were more than 2 years postsurgery. The postsurgical participants were found to have reduced chest dysphoria (the outcome) compared with a convenience and nonmatched comparison sample of nonsurgical transmasculine youth.
And a 2021 qualitative study of 30 transmale youth – about half of whom had undergone chest surgery – concluded that the postsurgical cohort experienced “tremendous” benefits in chest dysphoria and a range of psychological outcomes.
On this particular study, Ms. Clayton notes that “in my opinion, they did not provide enough detail for the reader to make an informed judgment regarding this latter claim.”
She goes on to discuss genital surgery, sometimes called full gender-affirming surgery (or “bottom surgery”), and says proponents of these operations point out that the main objections to them in minors is to “surgical sterilization, and people get super worked up about that ... it is a barrier we have to overcome, and I think we are going to.”
Ms. Clayton asserts that it seems “this barrier is already being overcome, as it has been reported that in the United States, genital surgery is being undertaken on gender dysphoric minors as young as 15 years old.”
Reflecting on the available evidence, Ms. Clayton highlights the significant methodological flaws that limit the extent to which surgery can be linked to short-term improved mental health outcomes and adds that information on long-term outcomes and rates of regret is unavailable.
She also asserts that the research fails to assess “a role for psychological interventions which could be utilized, as a least-harm intervention, until maturity is reached.”
Historical examples of experimental medicine
Ms. Clayton goes on to draw parallels with experimental medicine performed on homosexuals in the 20th century, highlighting the medical and surgical interventions, which included metrazol convulsive therapy, chemical castration with estrogens, surgical castration, clitoridectomy, brain operations, and aversive electrotherapy.
She also refers to the historical practice of hormonal treatment for “tall girls” and “short boys” between the 1960s and 1980s. Hormones were given to young people who did not have any medical reason underpinning their stature but were distressed, and society considered their height to have a negative social impact.
“With the encouragement of physicians and school nurses, enthusiastic media promotion, and pharmaceutical companies’ advertising, parents sought hormonal interventions,” she writes, adding that, at the time the hormones were considered safe, but long-term adverse effects emerged, including impaired fertility and increased risk of cancers.
“This seems another part of the story of medicine acting to reinforce society’s sex stereotypes, and for some patients it came at disastrous personal cost,” writes Ms. Clayton.
The gender-affirming approach is based on endorsing the adolescent’s stated gender identity with minimal questioning and “that they should be supported to undertake social transition, medical transition, masculinizing chest surgery, and, some also argue, genital surgery,” she writes.
Objectors to this approach pinpoint the “limited and low-quality evidence base for the benefits” but also “the irreversible and long-term adverse impacts of these treatments on fertility and sexual function, as well as on bone, brain, and cardiovascular functioning.”
Current studies of gender-affirming surgeries lack standardization
In their viewpoint, Dr. Agochukwu-Mmonu and colleagues state that use of a CED would not only help provide an evidence base but would also ensure better-informed policy access and coverage decisions to help standardize approaches to gender surgery in the United States.
Currently, they note, “Studies examining the mental health benefit for patients undergoing gender-affirming surgeries include measures that lack standardization, evaluate different interventions (that is, surgeries are rarely done with concurrent hormone administration), include dissimilar patient populations, and use different study designs.”
This difference in study design leads to variation in reported outcomes. Although many studies have shown benefit, others report that patients have unrealistic expectations or experience regret, Dr. Agochukwu-Mmonu and coauthors conclude.
CED provides an option that would enable informed decisions. “It allows the deliberate use of innovative therapies, explicit integration of transgender and nonbinary patient input, and ongoing systematic evaluation aimed to identify specific patient groups who would or would not benefit from their use.”
This leads back to Ms. Clayton’s central question around whether the gender-affirmative approach is a medical advance or dangerous medicine.
“Why are these experimental interventions, with inherent risks and scarce, low-quality evidence for benefits being implemented outside HREC-regulated clinical trial settings?’” she wonders.
Ms. Clayton has declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
Is the gender-affirmative treatment approach an example of “medicine continuing on its progressive march of improving human life” or “a manifestation of dangerous medicine that ... will cause more harm than benefit to vulnerable youths?” wonders an Australian psychiatrist in a newly published letter that addresses the controversial procedure of masculinizing chest surgery – a double mastectomy – in young people with gender dysphoria (GD).
Alison Clayton, MBBS, explores the evidence for masculinizing chest surgery and looks back at examples of “dangerous medicine” in the past century while looking forward, wondering how future medics will retrospectively view gender affirmative treatment, especially so-called “top” or masculinizing chest surgery, which is in actual fact a double mastectomy, in a letter published Nov. 22 in the Archives of Sexual Behavior.
“It is surprising that clinicians and researchers claim chest surgery for GD youth is an evidence-based intervention, rather than acknowledging it is an experimental treatment that requires more rigorous and human research ethics committee [HREC] approved research,” she writes.
“The medical profession needs to consider whether, in its championing of the gender-affirmative approach for GD youth, it is also acting brashly and making mistakes that will negatively impact some young people for the rest of their lives,” she continues.
Ms. Clayton, after many years of experience as a psychiatrist, has recently returned to postgraduate research into the history of 20th-century psychiatry at the School of Historical and Philosophical Studies, University of Melbourne.
Meanwhile, the authors of a viewpoint published online Dec. 1 in JAMA Surgery, agree with Ms. Clayton on the issue of a lack of long-term studies on which to base decisions, particularly when it comes to insurance coverage for gender surgeries in the United States.
Nnenaya Agochukwu-Mmonu, MD, and colleagues recommend use of the coverage with evidence development (CED) approach, which would, they say, provide a “rigorous evidence base for gender-affirming interventions and surgery while simultaneously allowing access and provisional coverage for these services.”
Threefold increase in gender-affirming surgeries in past decade
There has been a threefold rise in the rate of gender-affirming surgeries in the United States in the past decade, which can be attributed to increased recognition of gender dysphoria, decreasing social stigma toward these individuals, greater clinical experience, and expanding insurance coverage, according to Dr. Agochukwu-Mmonu, of the department of urology, NYU School of Medicine, and coauthors.
Ms. Clayton meanwhile notes that of the increasing number of adolescents being referred for treatment for gender dysphoria in the Western world, most were born female and many have “a history of psychiatric illness or neurodevelopmental disorders.”
Many of these youngsters also show a “high demand” for surgical removal of breasts, she adds, noting that this operation is being undertaken as routine treatment in patients as young as 13, with some clinicians arguing that “this surgery is an evidence-based intervention that improves mental health outcomes, and that it is discriminatory for it not to be available.”
She also notes that “chest dysphoria” is “a recently created term meaning discomfort with one’s breasts.” The term “breast” is therefore largely absent in publications talking about this surgery as it “may cause distress for transgender males,” to quote one source, Ms. Clayton says, and “this seems part of a broader pattern of removing this term from clinical language,” according to another article on the subject.
Ms. Clayton also says, “There are only a handful of published studies focusing on the potential benefits of masculinizing chest surgery,” and notes that these mostly report on surgery for individuals younger than 21 years old.
Significant methodological flaws in existing research
One study of 14 postsurgical youth (nine of whom were under 18 years) found that “all reported high aesthetic satisfaction and most self-reported low complication rates and improvement in mood.”
Another cross-sectional retrospective survey looked at 68 postsurgical transmasculine youth (72% of the eligible postsurgical population); 49% had surgery when younger than age 18, with the youngest being age 13 and the oldest age 24. At the time of the survey, only 14% of participants were more than 2 years postsurgery. The postsurgical participants were found to have reduced chest dysphoria (the outcome) compared with a convenience and nonmatched comparison sample of nonsurgical transmasculine youth.
And a 2021 qualitative study of 30 transmale youth – about half of whom had undergone chest surgery – concluded that the postsurgical cohort experienced “tremendous” benefits in chest dysphoria and a range of psychological outcomes.
On this particular study, Ms. Clayton notes that “in my opinion, they did not provide enough detail for the reader to make an informed judgment regarding this latter claim.”
She goes on to discuss genital surgery, sometimes called full gender-affirming surgery (or “bottom surgery”), and says proponents of these operations point out that the main objections to them in minors is to “surgical sterilization, and people get super worked up about that ... it is a barrier we have to overcome, and I think we are going to.”
Ms. Clayton asserts that it seems “this barrier is already being overcome, as it has been reported that in the United States, genital surgery is being undertaken on gender dysphoric minors as young as 15 years old.”
Reflecting on the available evidence, Ms. Clayton highlights the significant methodological flaws that limit the extent to which surgery can be linked to short-term improved mental health outcomes and adds that information on long-term outcomes and rates of regret is unavailable.
She also asserts that the research fails to assess “a role for psychological interventions which could be utilized, as a least-harm intervention, until maturity is reached.”
Historical examples of experimental medicine
Ms. Clayton goes on to draw parallels with experimental medicine performed on homosexuals in the 20th century, highlighting the medical and surgical interventions, which included metrazol convulsive therapy, chemical castration with estrogens, surgical castration, clitoridectomy, brain operations, and aversive electrotherapy.
She also refers to the historical practice of hormonal treatment for “tall girls” and “short boys” between the 1960s and 1980s. Hormones were given to young people who did not have any medical reason underpinning their stature but were distressed, and society considered their height to have a negative social impact.
“With the encouragement of physicians and school nurses, enthusiastic media promotion, and pharmaceutical companies’ advertising, parents sought hormonal interventions,” she writes, adding that, at the time the hormones were considered safe, but long-term adverse effects emerged, including impaired fertility and increased risk of cancers.
“This seems another part of the story of medicine acting to reinforce society’s sex stereotypes, and for some patients it came at disastrous personal cost,” writes Ms. Clayton.
The gender-affirming approach is based on endorsing the adolescent’s stated gender identity with minimal questioning and “that they should be supported to undertake social transition, medical transition, masculinizing chest surgery, and, some also argue, genital surgery,” she writes.
Objectors to this approach pinpoint the “limited and low-quality evidence base for the benefits” but also “the irreversible and long-term adverse impacts of these treatments on fertility and sexual function, as well as on bone, brain, and cardiovascular functioning.”
Current studies of gender-affirming surgeries lack standardization
In their viewpoint, Dr. Agochukwu-Mmonu and colleagues state that use of a CED would not only help provide an evidence base but would also ensure better-informed policy access and coverage decisions to help standardize approaches to gender surgery in the United States.
Currently, they note, “Studies examining the mental health benefit for patients undergoing gender-affirming surgeries include measures that lack standardization, evaluate different interventions (that is, surgeries are rarely done with concurrent hormone administration), include dissimilar patient populations, and use different study designs.”
This difference in study design leads to variation in reported outcomes. Although many studies have shown benefit, others report that patients have unrealistic expectations or experience regret, Dr. Agochukwu-Mmonu and coauthors conclude.
CED provides an option that would enable informed decisions. “It allows the deliberate use of innovative therapies, explicit integration of transgender and nonbinary patient input, and ongoing systematic evaluation aimed to identify specific patient groups who would or would not benefit from their use.”
This leads back to Ms. Clayton’s central question around whether the gender-affirmative approach is a medical advance or dangerous medicine.
“Why are these experimental interventions, with inherent risks and scarce, low-quality evidence for benefits being implemented outside HREC-regulated clinical trial settings?’” she wonders.
Ms. Clayton has declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA SURGERY
HPV vaccines reduce cervical cancer rates in young females
Two different studies have found that, provided young females are immunized with the human papilloma virus (HPV) vaccine at a young enough age, both the incidence of and mortality from cervical cancer can be dramatically curtailed, data from the United Kingdom and to a lesser extent, the United States indicate.
In the U.K. study, published online in The Lancet, researchers showed that the national vaccination program against HPV, initiated in England in 2008, has all but eradicated cervical cancer and cervical intraepithelial neoplasia (CIN3) in young girls who received the vaccine at the age of 12 and 13 years (school year 8) prior to their sexual debut.
In this age group, cervical cancer rates were 87% lower than rates among previously nonvaccinated generations, while CIN3 rates were reduced by 97%, as researchers report. “It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding,” he added.
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, UK Health Security Agency, London, said in the same statement.
“This represents an important step forward in cervical cancer prevention, and we hope that these new results encourage uptake as the success of the vaccination programme relies not only on the efficacy of the vaccine but also the proportion of the population vaccinated,” she added.
Vanessa Saliba, MD, a consultant epidemiologist for the UK Health Security Agency, agreed, adding that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.”
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she reemphasized.
British HPV program
When initiated in 2008, the national HPV vaccination program used the bivalent, Cervarix vaccine against HPV 16 and 18. As researchers noted, these two HPV types are responsible for 70%-80% of all cervical cancers in England.
However, in 2012, the program switched to the quadrivalent HPV vaccine (Gardasil) which is also effective against two additional HPV types, 6 and 11, both of which cause genital warts. The program also originally recommended the three-dose regimen for both HPV vaccines.
Now, only two doses of the vaccine are given to girls under the age of 15 even though it has been shown that a single dose of the HPV vaccine provides good protection against persistent infection, with efficacy rates that are similar to that of three doses, as the authors point out.
Among the cohort eligible for vaccination at 12 or 13 years of age, 89% received at least one dose of the HPV vaccine while 85% of the same age group received all three shots.
Cancer registry
Data from a population-based cancer registry was used to estimate the early effect of the bivalent HPV program on the incidence of cervical cancer and CIN3 in England between January 2006 and June 2019. During the study interval, there were 27,946 diagnoses of cervical cancer and 318,058 diagnoses of CIN3, lead author Milena Falcaro, MD, King’s College London, and colleagues report. Participants were then analyzed separately according to their age at the time of vaccination and the incidence rates calculated for both cervical cancer and CIN3 in the three separate groups.
For slightly older girls who received the vaccine between 14 and 16 years of age (school year 10-11), cervical cancer was reduced by 62% while CIN3 rates were reduced by 75%. For those who received the vaccine between 16 and 18 years of age (school year 12-13), cervical cancer rates were reduced by 34% while CIN3 rates were reduced by 39%, study authors add.
Indeed, the authors estimate that by June 2019 there were approximately 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would otherwise have been expected in the vaccinated population in England.
The authors acknowledge that cervical cancer is rare in young women and vaccinated populations are still young. For example, the youngest recipients would have been immunized at the age of 12 in 2008 and would still be only 23 years old in 2019 when the study ended.
Thus, the authors emphasize that, because the vaccinated populations are still young, it’s too early to assess the full effect of HPV vaccination on cervical cancer rates.
Asked to comment on the study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, pointed out that results from the British study are very similar to those from a Swedish study assessing the effect of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. As an oncologist who has been treating cervical cancer for 40 years – particularly advanced cervical cancer – “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful,” he stressed.
Editorial commentary
Commenting on the findings, editorialists Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania, point out that published reports evaluating the effect of HPV vaccination on cervical cancer rates have been scarce until now.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by the WHO [World Health Organization],” the editorialists add.
Dr. Cruickshank and Dr. Grigore also suggest that the effect HPV vaccination is having on cervical cancer rates as shown in this study should also stimulate vaccination programs in low- and middle-income countries where cervical cancer is a far greater public health issue than it is in countries with established systems of vaccination and screening.
HPV vaccination in the United States
The HPV vaccination program is similarly reducing the incidence of and mortality from cervical cancer among younger women in the United States who are most likely to have received the vaccine. As reported by lead author, Justin Barnes, MD, Washington University, St. Louis, the incidence of cervical cancer dropped by 37.7% from 2001 through 2005 to 2010 through 2017 in girls and young women between 15 and 24 years of age.
The U.S. study was published online in JAMA Pediatrics.
“HPV vaccine coverage in the U.S. has improved over the last few years although it was quite poor for many years,” senior author of the U.K. study, Peter Sasieni, MD, King’s College London, said in an interview. “Thus, one would anticipate a lower impact on the population in the U.S., because vaccine uptake, particularly in those aged 11-14 years was so much lower than it was in the U.K.,” he noted.
SEER databases
National age-adjusted cervical cancer incidence and mortality data from January 2001 through December 2017 for women and girls between 15 and 39 years of age were obtained from the combined Surveillance, Epidemiology, and End Results as well as the National Program of Cancer Registries databases. Mortality data was obtained from the National Center for Health Statistics.
Investigators then compared percentage changes in the incidence of and mortality from cervical cancer from January 2001 through December 2005 during the prevaccination years to that observed between January 2010 through December 2017 during the postvaccination years. They also compared incidence and mortality rates in three different cohorts: females between 15 and 24 years of age, those between 25 and 29 years of age, and those between 30 and 39 years of age.
“The older two groups were included as comparison, given their low vaccination rates,” the authors explained. Results showed that, during the same study interval from 2001 through 2005 to 2010 through 2017, the incidence of cervical cancer dropped by only 16.1% in women between 25 and 29 years of age and by only 8% for women between 30 and 39 years of age, the investigators report.
Reductions in mortality from cervical cancer were only strikingly so in the youngest age group of females between 15 and 24 years of age, among whom there was a 43.3% reduction in mortality from 2001-2005 to 2010-2017, as Dr. Barnes and colleagues note.
This pattern changed substantially in women between the ages of 25 and 29, among whom there was a 4.3% increase in mortality from cervical cancer during the same study interval and a small, 4.7% reduction among women between 30 and 39 years of age, investigators add. In actual numbers, mortality rates from cervical cancer were very low at only 0.6 per 100,000 in females between 15 and 24 years of age.
This compared to a mortality rate of 0.57 per 100,000 in women between 25 and 29 years of age and 1.89 per 100,000 in the oldest age group. “These nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes notes.
“Thus, the current study adds to knowledge by quantitatively comparing changes in cervical cancer incidence by age-based vaccine eligibility and providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators add.
However, as the authors also point out, while the reduction in mortality from cervical cancer associated with HPV vaccination may translate to older age groups as HPV-vaccinated cohorts age, “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” they caution, “and efforts to further improve vaccination uptake remain important.”
None of the authors or the editorialists had any conflicts of interest to declare.
Two different studies have found that, provided young females are immunized with the human papilloma virus (HPV) vaccine at a young enough age, both the incidence of and mortality from cervical cancer can be dramatically curtailed, data from the United Kingdom and to a lesser extent, the United States indicate.
In the U.K. study, published online in The Lancet, researchers showed that the national vaccination program against HPV, initiated in England in 2008, has all but eradicated cervical cancer and cervical intraepithelial neoplasia (CIN3) in young girls who received the vaccine at the age of 12 and 13 years (school year 8) prior to their sexual debut.
In this age group, cervical cancer rates were 87% lower than rates among previously nonvaccinated generations, while CIN3 rates were reduced by 97%, as researchers report. “It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding,” he added.
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, UK Health Security Agency, London, said in the same statement.
“This represents an important step forward in cervical cancer prevention, and we hope that these new results encourage uptake as the success of the vaccination programme relies not only on the efficacy of the vaccine but also the proportion of the population vaccinated,” she added.
Vanessa Saliba, MD, a consultant epidemiologist for the UK Health Security Agency, agreed, adding that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.”
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she reemphasized.
British HPV program
When initiated in 2008, the national HPV vaccination program used the bivalent, Cervarix vaccine against HPV 16 and 18. As researchers noted, these two HPV types are responsible for 70%-80% of all cervical cancers in England.
However, in 2012, the program switched to the quadrivalent HPV vaccine (Gardasil) which is also effective against two additional HPV types, 6 and 11, both of which cause genital warts. The program also originally recommended the three-dose regimen for both HPV vaccines.
Now, only two doses of the vaccine are given to girls under the age of 15 even though it has been shown that a single dose of the HPV vaccine provides good protection against persistent infection, with efficacy rates that are similar to that of three doses, as the authors point out.
Among the cohort eligible for vaccination at 12 or 13 years of age, 89% received at least one dose of the HPV vaccine while 85% of the same age group received all three shots.
Cancer registry
Data from a population-based cancer registry was used to estimate the early effect of the bivalent HPV program on the incidence of cervical cancer and CIN3 in England between January 2006 and June 2019. During the study interval, there were 27,946 diagnoses of cervical cancer and 318,058 diagnoses of CIN3, lead author Milena Falcaro, MD, King’s College London, and colleagues report. Participants were then analyzed separately according to their age at the time of vaccination and the incidence rates calculated for both cervical cancer and CIN3 in the three separate groups.
For slightly older girls who received the vaccine between 14 and 16 years of age (school year 10-11), cervical cancer was reduced by 62% while CIN3 rates were reduced by 75%. For those who received the vaccine between 16 and 18 years of age (school year 12-13), cervical cancer rates were reduced by 34% while CIN3 rates were reduced by 39%, study authors add.
Indeed, the authors estimate that by June 2019 there were approximately 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would otherwise have been expected in the vaccinated population in England.
The authors acknowledge that cervical cancer is rare in young women and vaccinated populations are still young. For example, the youngest recipients would have been immunized at the age of 12 in 2008 and would still be only 23 years old in 2019 when the study ended.
Thus, the authors emphasize that, because the vaccinated populations are still young, it’s too early to assess the full effect of HPV vaccination on cervical cancer rates.
Asked to comment on the study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, pointed out that results from the British study are very similar to those from a Swedish study assessing the effect of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. As an oncologist who has been treating cervical cancer for 40 years – particularly advanced cervical cancer – “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful,” he stressed.
Editorial commentary
Commenting on the findings, editorialists Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania, point out that published reports evaluating the effect of HPV vaccination on cervical cancer rates have been scarce until now.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by the WHO [World Health Organization],” the editorialists add.
Dr. Cruickshank and Dr. Grigore also suggest that the effect HPV vaccination is having on cervical cancer rates as shown in this study should also stimulate vaccination programs in low- and middle-income countries where cervical cancer is a far greater public health issue than it is in countries with established systems of vaccination and screening.
HPV vaccination in the United States
The HPV vaccination program is similarly reducing the incidence of and mortality from cervical cancer among younger women in the United States who are most likely to have received the vaccine. As reported by lead author, Justin Barnes, MD, Washington University, St. Louis, the incidence of cervical cancer dropped by 37.7% from 2001 through 2005 to 2010 through 2017 in girls and young women between 15 and 24 years of age.
The U.S. study was published online in JAMA Pediatrics.
“HPV vaccine coverage in the U.S. has improved over the last few years although it was quite poor for many years,” senior author of the U.K. study, Peter Sasieni, MD, King’s College London, said in an interview. “Thus, one would anticipate a lower impact on the population in the U.S., because vaccine uptake, particularly in those aged 11-14 years was so much lower than it was in the U.K.,” he noted.
SEER databases
National age-adjusted cervical cancer incidence and mortality data from January 2001 through December 2017 for women and girls between 15 and 39 years of age were obtained from the combined Surveillance, Epidemiology, and End Results as well as the National Program of Cancer Registries databases. Mortality data was obtained from the National Center for Health Statistics.
Investigators then compared percentage changes in the incidence of and mortality from cervical cancer from January 2001 through December 2005 during the prevaccination years to that observed between January 2010 through December 2017 during the postvaccination years. They also compared incidence and mortality rates in three different cohorts: females between 15 and 24 years of age, those between 25 and 29 years of age, and those between 30 and 39 years of age.
“The older two groups were included as comparison, given their low vaccination rates,” the authors explained. Results showed that, during the same study interval from 2001 through 2005 to 2010 through 2017, the incidence of cervical cancer dropped by only 16.1% in women between 25 and 29 years of age and by only 8% for women between 30 and 39 years of age, the investigators report.
Reductions in mortality from cervical cancer were only strikingly so in the youngest age group of females between 15 and 24 years of age, among whom there was a 43.3% reduction in mortality from 2001-2005 to 2010-2017, as Dr. Barnes and colleagues note.
This pattern changed substantially in women between the ages of 25 and 29, among whom there was a 4.3% increase in mortality from cervical cancer during the same study interval and a small, 4.7% reduction among women between 30 and 39 years of age, investigators add. In actual numbers, mortality rates from cervical cancer were very low at only 0.6 per 100,000 in females between 15 and 24 years of age.
This compared to a mortality rate of 0.57 per 100,000 in women between 25 and 29 years of age and 1.89 per 100,000 in the oldest age group. “These nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes notes.
“Thus, the current study adds to knowledge by quantitatively comparing changes in cervical cancer incidence by age-based vaccine eligibility and providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators add.
However, as the authors also point out, while the reduction in mortality from cervical cancer associated with HPV vaccination may translate to older age groups as HPV-vaccinated cohorts age, “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” they caution, “and efforts to further improve vaccination uptake remain important.”
None of the authors or the editorialists had any conflicts of interest to declare.
Two different studies have found that, provided young females are immunized with the human papilloma virus (HPV) vaccine at a young enough age, both the incidence of and mortality from cervical cancer can be dramatically curtailed, data from the United Kingdom and to a lesser extent, the United States indicate.
In the U.K. study, published online in The Lancet, researchers showed that the national vaccination program against HPV, initiated in England in 2008, has all but eradicated cervical cancer and cervical intraepithelial neoplasia (CIN3) in young girls who received the vaccine at the age of 12 and 13 years (school year 8) prior to their sexual debut.
In this age group, cervical cancer rates were 87% lower than rates among previously nonvaccinated generations, while CIN3 rates were reduced by 97%, as researchers report. “It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding,” he added.
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, UK Health Security Agency, London, said in the same statement.
“This represents an important step forward in cervical cancer prevention, and we hope that these new results encourage uptake as the success of the vaccination programme relies not only on the efficacy of the vaccine but also the proportion of the population vaccinated,” she added.
Vanessa Saliba, MD, a consultant epidemiologist for the UK Health Security Agency, agreed, adding that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.”
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she reemphasized.
British HPV program
When initiated in 2008, the national HPV vaccination program used the bivalent, Cervarix vaccine against HPV 16 and 18. As researchers noted, these two HPV types are responsible for 70%-80% of all cervical cancers in England.
However, in 2012, the program switched to the quadrivalent HPV vaccine (Gardasil) which is also effective against two additional HPV types, 6 and 11, both of which cause genital warts. The program also originally recommended the three-dose regimen for both HPV vaccines.
Now, only two doses of the vaccine are given to girls under the age of 15 even though it has been shown that a single dose of the HPV vaccine provides good protection against persistent infection, with efficacy rates that are similar to that of three doses, as the authors point out.
Among the cohort eligible for vaccination at 12 or 13 years of age, 89% received at least one dose of the HPV vaccine while 85% of the same age group received all three shots.
Cancer registry
Data from a population-based cancer registry was used to estimate the early effect of the bivalent HPV program on the incidence of cervical cancer and CIN3 in England between January 2006 and June 2019. During the study interval, there were 27,946 diagnoses of cervical cancer and 318,058 diagnoses of CIN3, lead author Milena Falcaro, MD, King’s College London, and colleagues report. Participants were then analyzed separately according to their age at the time of vaccination and the incidence rates calculated for both cervical cancer and CIN3 in the three separate groups.
For slightly older girls who received the vaccine between 14 and 16 years of age (school year 10-11), cervical cancer was reduced by 62% while CIN3 rates were reduced by 75%. For those who received the vaccine between 16 and 18 years of age (school year 12-13), cervical cancer rates were reduced by 34% while CIN3 rates were reduced by 39%, study authors add.
Indeed, the authors estimate that by June 2019 there were approximately 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would otherwise have been expected in the vaccinated population in England.
The authors acknowledge that cervical cancer is rare in young women and vaccinated populations are still young. For example, the youngest recipients would have been immunized at the age of 12 in 2008 and would still be only 23 years old in 2019 when the study ended.
Thus, the authors emphasize that, because the vaccinated populations are still young, it’s too early to assess the full effect of HPV vaccination on cervical cancer rates.
Asked to comment on the study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, pointed out that results from the British study are very similar to those from a Swedish study assessing the effect of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. As an oncologist who has been treating cervical cancer for 40 years – particularly advanced cervical cancer – “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful,” he stressed.
Editorial commentary
Commenting on the findings, editorialists Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania, point out that published reports evaluating the effect of HPV vaccination on cervical cancer rates have been scarce until now.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by the WHO [World Health Organization],” the editorialists add.
Dr. Cruickshank and Dr. Grigore also suggest that the effect HPV vaccination is having on cervical cancer rates as shown in this study should also stimulate vaccination programs in low- and middle-income countries where cervical cancer is a far greater public health issue than it is in countries with established systems of vaccination and screening.
HPV vaccination in the United States
The HPV vaccination program is similarly reducing the incidence of and mortality from cervical cancer among younger women in the United States who are most likely to have received the vaccine. As reported by lead author, Justin Barnes, MD, Washington University, St. Louis, the incidence of cervical cancer dropped by 37.7% from 2001 through 2005 to 2010 through 2017 in girls and young women between 15 and 24 years of age.
The U.S. study was published online in JAMA Pediatrics.
“HPV vaccine coverage in the U.S. has improved over the last few years although it was quite poor for many years,” senior author of the U.K. study, Peter Sasieni, MD, King’s College London, said in an interview. “Thus, one would anticipate a lower impact on the population in the U.S., because vaccine uptake, particularly in those aged 11-14 years was so much lower than it was in the U.K.,” he noted.
SEER databases
National age-adjusted cervical cancer incidence and mortality data from January 2001 through December 2017 for women and girls between 15 and 39 years of age were obtained from the combined Surveillance, Epidemiology, and End Results as well as the National Program of Cancer Registries databases. Mortality data was obtained from the National Center for Health Statistics.
Investigators then compared percentage changes in the incidence of and mortality from cervical cancer from January 2001 through December 2005 during the prevaccination years to that observed between January 2010 through December 2017 during the postvaccination years. They also compared incidence and mortality rates in three different cohorts: females between 15 and 24 years of age, those between 25 and 29 years of age, and those between 30 and 39 years of age.
“The older two groups were included as comparison, given their low vaccination rates,” the authors explained. Results showed that, during the same study interval from 2001 through 2005 to 2010 through 2017, the incidence of cervical cancer dropped by only 16.1% in women between 25 and 29 years of age and by only 8% for women between 30 and 39 years of age, the investigators report.
Reductions in mortality from cervical cancer were only strikingly so in the youngest age group of females between 15 and 24 years of age, among whom there was a 43.3% reduction in mortality from 2001-2005 to 2010-2017, as Dr. Barnes and colleagues note.
This pattern changed substantially in women between the ages of 25 and 29, among whom there was a 4.3% increase in mortality from cervical cancer during the same study interval and a small, 4.7% reduction among women between 30 and 39 years of age, investigators add. In actual numbers, mortality rates from cervical cancer were very low at only 0.6 per 100,000 in females between 15 and 24 years of age.
This compared to a mortality rate of 0.57 per 100,000 in women between 25 and 29 years of age and 1.89 per 100,000 in the oldest age group. “These nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes notes.
“Thus, the current study adds to knowledge by quantitatively comparing changes in cervical cancer incidence by age-based vaccine eligibility and providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators add.
However, as the authors also point out, while the reduction in mortality from cervical cancer associated with HPV vaccination may translate to older age groups as HPV-vaccinated cohorts age, “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” they caution, “and efforts to further improve vaccination uptake remain important.”
None of the authors or the editorialists had any conflicts of interest to declare.
First Omicron variant case identified in U.S.
He or she was fully vaccinated against COVID-19 and experienced only “mild symptoms that are improving,” officials with the Centers for Disease Control and Prevention said.
The patient, who was not named in the CDC’s announcement of the first U.S. case of the Omicron variant Dec. 1, is self-quarantining.
“All close contacts have been contacted and have tested negative,” officials said.
The announcement comes as no surprise to many as the Omicron variant, first identified in South Africa, has been reported in countries around the world in recent days. Hong Kong, the United Kingdom, and Germany each reported this variant, as have Italy and the Netherlands. Over the weekend, the first North American cases were identified in Canada.
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, announced over the weekend that this newest variant was likely already in the United States, telling ABC’s This Week its appearance here was “inevitable.”
Similar to previous variants, this new strain likely started circulating in the United States before scientists could do genetic tests to confirm its presence.
The World Health Organization named Omicron a “variant of concern” on Nov. 26, even though much remains unknown about how well it spreads, how severe it can be, and how it may resist vaccines. In the meantime, the United States enacted travel bans from multiple South African countries.
It remains to be seen if Omicron will follow the pattern of the Delta variant, which was first identified in the United States in May and became the dominant strain by July. It’s also possible it will follow the path taken by the Mu variant. Mu emerged in March and April to much concern, only to fizzle out by September because it was unable to compete with the Delta variant.
A version of this article first appeared on WebMD.com.
He or she was fully vaccinated against COVID-19 and experienced only “mild symptoms that are improving,” officials with the Centers for Disease Control and Prevention said.
The patient, who was not named in the CDC’s announcement of the first U.S. case of the Omicron variant Dec. 1, is self-quarantining.
“All close contacts have been contacted and have tested negative,” officials said.
The announcement comes as no surprise to many as the Omicron variant, first identified in South Africa, has been reported in countries around the world in recent days. Hong Kong, the United Kingdom, and Germany each reported this variant, as have Italy and the Netherlands. Over the weekend, the first North American cases were identified in Canada.
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, announced over the weekend that this newest variant was likely already in the United States, telling ABC’s This Week its appearance here was “inevitable.”
Similar to previous variants, this new strain likely started circulating in the United States before scientists could do genetic tests to confirm its presence.
The World Health Organization named Omicron a “variant of concern” on Nov. 26, even though much remains unknown about how well it spreads, how severe it can be, and how it may resist vaccines. In the meantime, the United States enacted travel bans from multiple South African countries.
It remains to be seen if Omicron will follow the pattern of the Delta variant, which was first identified in the United States in May and became the dominant strain by July. It’s also possible it will follow the path taken by the Mu variant. Mu emerged in March and April to much concern, only to fizzle out by September because it was unable to compete with the Delta variant.
A version of this article first appeared on WebMD.com.
He or she was fully vaccinated against COVID-19 and experienced only “mild symptoms that are improving,” officials with the Centers for Disease Control and Prevention said.
The patient, who was not named in the CDC’s announcement of the first U.S. case of the Omicron variant Dec. 1, is self-quarantining.
“All close contacts have been contacted and have tested negative,” officials said.
The announcement comes as no surprise to many as the Omicron variant, first identified in South Africa, has been reported in countries around the world in recent days. Hong Kong, the United Kingdom, and Germany each reported this variant, as have Italy and the Netherlands. Over the weekend, the first North American cases were identified in Canada.
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, announced over the weekend that this newest variant was likely already in the United States, telling ABC’s This Week its appearance here was “inevitable.”
Similar to previous variants, this new strain likely started circulating in the United States before scientists could do genetic tests to confirm its presence.
The World Health Organization named Omicron a “variant of concern” on Nov. 26, even though much remains unknown about how well it spreads, how severe it can be, and how it may resist vaccines. In the meantime, the United States enacted travel bans from multiple South African countries.
It remains to be seen if Omicron will follow the pattern of the Delta variant, which was first identified in the United States in May and became the dominant strain by July. It’s also possible it will follow the path taken by the Mu variant. Mu emerged in March and April to much concern, only to fizzle out by September because it was unable to compete with the Delta variant.
A version of this article first appeared on WebMD.com.
Moderna warns of material drop in vaccine efficacy against Omicron
“There is no world, I think, where [the effectiveness] is the same level … we had with Delta,” Stephane Bancel told the Financial Times .
“I think it’s going to be a material drop,” he said. “I just don’t know how much, because we need to wait for the data. But all the scientists I’ve talked to … are like, ‘This is not going to be good.’”
Vaccine companies are now studying whether the new Omicron variant could evade the current shots. Some data is expected in about 2 weeks.
Mr. Bancel said that if a new vaccine is needed, it could take several months to produce at scale. He estimated that Moderna could make billions of vaccine doses in 2022.
“[Moderna] and Pfizer cannot get a billion doses next week. The math doesn’t work,” he said. “But could we get the billion doses out by the summer? Sure.”
The news caused some panic on Nov. 30, prompting financial markets to fall sharply, according to Reuters. But the markets recovered after European officials gave a more reassuring outlook.
“Even if the new variant becomes more widespread, the vaccines we have will continue to provide protection,” Emer Cooke, executive director of the European Medicines Agency, told the European Parliament.
Mr. Cooke said the agency could approve new vaccines that target the Omicron variant within 3 to 4 months, if needed. Moderna and Pfizer have announced they are beginning to tailor a shot to address the Omicron variant in case the data shows they are necessary.
Also on Nov. 30, the European Centre for Disease Prevention and Control announced that 42 Omicron cases had been identified in 10 European Union countries, according to Reuters.
The cases were mild or had no symptoms, although they were found in younger people who may have mild or no symptoms anyway.
“For the assessment of whether [Omicron] escapes immunity, we still have to wait until investigations in the laboratories with [blood samples] from people who have recovered have been carried out,” Andrea Ammon, MD, chair of the agency, said during an online conference.
The University of Oxford, which developed a COVID-19 vaccine with AstraZeneca, said Nov. 30 that there’s no evidence that vaccines won’t prevent severe disease from the Omicron variant, according to Reuters.
“Despite the appearance of new variants over the past year, vaccines have continued to provide very high levels of protection against severe disease and there is no evidence so far that Omicron is any different,” the university said in a statement. “However, we have the necessary tools and processes in place for rapid development of an updated COVID-19 vaccine if it should be necessary.”
A version of this article first appeared on WebMD.com.
“There is no world, I think, where [the effectiveness] is the same level … we had with Delta,” Stephane Bancel told the Financial Times .
“I think it’s going to be a material drop,” he said. “I just don’t know how much, because we need to wait for the data. But all the scientists I’ve talked to … are like, ‘This is not going to be good.’”
Vaccine companies are now studying whether the new Omicron variant could evade the current shots. Some data is expected in about 2 weeks.
Mr. Bancel said that if a new vaccine is needed, it could take several months to produce at scale. He estimated that Moderna could make billions of vaccine doses in 2022.
“[Moderna] and Pfizer cannot get a billion doses next week. The math doesn’t work,” he said. “But could we get the billion doses out by the summer? Sure.”
The news caused some panic on Nov. 30, prompting financial markets to fall sharply, according to Reuters. But the markets recovered after European officials gave a more reassuring outlook.
“Even if the new variant becomes more widespread, the vaccines we have will continue to provide protection,” Emer Cooke, executive director of the European Medicines Agency, told the European Parliament.
Mr. Cooke said the agency could approve new vaccines that target the Omicron variant within 3 to 4 months, if needed. Moderna and Pfizer have announced they are beginning to tailor a shot to address the Omicron variant in case the data shows they are necessary.
Also on Nov. 30, the European Centre for Disease Prevention and Control announced that 42 Omicron cases had been identified in 10 European Union countries, according to Reuters.
The cases were mild or had no symptoms, although they were found in younger people who may have mild or no symptoms anyway.
“For the assessment of whether [Omicron] escapes immunity, we still have to wait until investigations in the laboratories with [blood samples] from people who have recovered have been carried out,” Andrea Ammon, MD, chair of the agency, said during an online conference.
The University of Oxford, which developed a COVID-19 vaccine with AstraZeneca, said Nov. 30 that there’s no evidence that vaccines won’t prevent severe disease from the Omicron variant, according to Reuters.
“Despite the appearance of new variants over the past year, vaccines have continued to provide very high levels of protection against severe disease and there is no evidence so far that Omicron is any different,” the university said in a statement. “However, we have the necessary tools and processes in place for rapid development of an updated COVID-19 vaccine if it should be necessary.”
A version of this article first appeared on WebMD.com.
“There is no world, I think, where [the effectiveness] is the same level … we had with Delta,” Stephane Bancel told the Financial Times .
“I think it’s going to be a material drop,” he said. “I just don’t know how much, because we need to wait for the data. But all the scientists I’ve talked to … are like, ‘This is not going to be good.’”
Vaccine companies are now studying whether the new Omicron variant could evade the current shots. Some data is expected in about 2 weeks.
Mr. Bancel said that if a new vaccine is needed, it could take several months to produce at scale. He estimated that Moderna could make billions of vaccine doses in 2022.
“[Moderna] and Pfizer cannot get a billion doses next week. The math doesn’t work,” he said. “But could we get the billion doses out by the summer? Sure.”
The news caused some panic on Nov. 30, prompting financial markets to fall sharply, according to Reuters. But the markets recovered after European officials gave a more reassuring outlook.
“Even if the new variant becomes more widespread, the vaccines we have will continue to provide protection,” Emer Cooke, executive director of the European Medicines Agency, told the European Parliament.
Mr. Cooke said the agency could approve new vaccines that target the Omicron variant within 3 to 4 months, if needed. Moderna and Pfizer have announced they are beginning to tailor a shot to address the Omicron variant in case the data shows they are necessary.
Also on Nov. 30, the European Centre for Disease Prevention and Control announced that 42 Omicron cases had been identified in 10 European Union countries, according to Reuters.
The cases were mild or had no symptoms, although they were found in younger people who may have mild or no symptoms anyway.
“For the assessment of whether [Omicron] escapes immunity, we still have to wait until investigations in the laboratories with [blood samples] from people who have recovered have been carried out,” Andrea Ammon, MD, chair of the agency, said during an online conference.
The University of Oxford, which developed a COVID-19 vaccine with AstraZeneca, said Nov. 30 that there’s no evidence that vaccines won’t prevent severe disease from the Omicron variant, according to Reuters.
“Despite the appearance of new variants over the past year, vaccines have continued to provide very high levels of protection against severe disease and there is no evidence so far that Omicron is any different,” the university said in a statement. “However, we have the necessary tools and processes in place for rapid development of an updated COVID-19 vaccine if it should be necessary.”
A version of this article first appeared on WebMD.com.
Children and COVID: New cases, vaccinations both decline
States reported 131,828 new pediatric cases for the week of Nov. 19-25, a decline of 7.1% over the previous week but still enough to surpass 100,000 for the 16th consecutive week. The weekly count had risen for 3 straight weeks since the last decrease in late October, the American Academy of Pediatrics and the Children’s Hospital Association said Nov. 30 in their weekly COVID report.
The AAP/CHA analysis, based on data from state and territorial health departments, puts the total number of cases in children at 6.9 million since the pandemic began, representing 17.0% of cases in Americans of all ages. The Centers for Disease Control and Prevention, which uses an age limit of 18 years to define a child, unlike some states, reports numbers of 6.1 million and 15.5%.
New vaccinations among the youngest eligible children, those aged 5-11 years, were down for the second week in a row after reaching almost 1.7 million during the first full week after approval on Nov. 2. Since then, the vaccination counts have been 1.2 million (Nov. 16-22) and 333,000 (Nov. 23-29), the CDC said on its COVID Data Tracker. A similar drop in the last week – from 127,000 to just 50,000 – also was seen for those aged 12-17 years.
Altogether, 14.2% of children aged 5-11, almost 4.1 million individuals, have received at least one dose of the vaccine, compared with 59.0% (10 million) of the 12- to 15-year-olds and 65.2% (5.5 million) of those aged 16-17. Just under 1% of the youngest group has been fully vaccinated, versus 49.0% and 55.8% for the older children, the CDC said.
It has been reported that Pfizer and BioNTech, which produce the only COVID vaccine approved for children, are planning to apply to the Food and Drug Administration during the first week of December for authorization for a booster dose for 16- and 17-year-olds.
States reported 131,828 new pediatric cases for the week of Nov. 19-25, a decline of 7.1% over the previous week but still enough to surpass 100,000 for the 16th consecutive week. The weekly count had risen for 3 straight weeks since the last decrease in late October, the American Academy of Pediatrics and the Children’s Hospital Association said Nov. 30 in their weekly COVID report.
The AAP/CHA analysis, based on data from state and territorial health departments, puts the total number of cases in children at 6.9 million since the pandemic began, representing 17.0% of cases in Americans of all ages. The Centers for Disease Control and Prevention, which uses an age limit of 18 years to define a child, unlike some states, reports numbers of 6.1 million and 15.5%.
New vaccinations among the youngest eligible children, those aged 5-11 years, were down for the second week in a row after reaching almost 1.7 million during the first full week after approval on Nov. 2. Since then, the vaccination counts have been 1.2 million (Nov. 16-22) and 333,000 (Nov. 23-29), the CDC said on its COVID Data Tracker. A similar drop in the last week – from 127,000 to just 50,000 – also was seen for those aged 12-17 years.
Altogether, 14.2% of children aged 5-11, almost 4.1 million individuals, have received at least one dose of the vaccine, compared with 59.0% (10 million) of the 12- to 15-year-olds and 65.2% (5.5 million) of those aged 16-17. Just under 1% of the youngest group has been fully vaccinated, versus 49.0% and 55.8% for the older children, the CDC said.
It has been reported that Pfizer and BioNTech, which produce the only COVID vaccine approved for children, are planning to apply to the Food and Drug Administration during the first week of December for authorization for a booster dose for 16- and 17-year-olds.
States reported 131,828 new pediatric cases for the week of Nov. 19-25, a decline of 7.1% over the previous week but still enough to surpass 100,000 for the 16th consecutive week. The weekly count had risen for 3 straight weeks since the last decrease in late October, the American Academy of Pediatrics and the Children’s Hospital Association said Nov. 30 in their weekly COVID report.
The AAP/CHA analysis, based on data from state and territorial health departments, puts the total number of cases in children at 6.9 million since the pandemic began, representing 17.0% of cases in Americans of all ages. The Centers for Disease Control and Prevention, which uses an age limit of 18 years to define a child, unlike some states, reports numbers of 6.1 million and 15.5%.
New vaccinations among the youngest eligible children, those aged 5-11 years, were down for the second week in a row after reaching almost 1.7 million during the first full week after approval on Nov. 2. Since then, the vaccination counts have been 1.2 million (Nov. 16-22) and 333,000 (Nov. 23-29), the CDC said on its COVID Data Tracker. A similar drop in the last week – from 127,000 to just 50,000 – also was seen for those aged 12-17 years.
Altogether, 14.2% of children aged 5-11, almost 4.1 million individuals, have received at least one dose of the vaccine, compared with 59.0% (10 million) of the 12- to 15-year-olds and 65.2% (5.5 million) of those aged 16-17. Just under 1% of the youngest group has been fully vaccinated, versus 49.0% and 55.8% for the older children, the CDC said.
It has been reported that Pfizer and BioNTech, which produce the only COVID vaccine approved for children, are planning to apply to the Food and Drug Administration during the first week of December for authorization for a booster dose for 16- and 17-year-olds.
Association of height, BMI, and AD in young children may be transient
The , 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 , 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 , 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.
FROM JAMA DERMATOLOGY
Fauci: Omicron ‘very different from other variants’
The newly detected Omicron COVID-19 variant may be highly infectious and less responsive to available vaccines than other variants, but it is too early to know how it compares to the Delta variant, top infectious disease official Anthony S. Fauci, MD, said Nov. 30.
Dr. Fauci, speaking at a White House COVID-19 briefing, said there’s a “very unusual constellation of changes” across the COVID-19 genome that indicates it is unlike any variant we have seen so far.
“This mutational profile is very different from other variants of interest and concern, and although some mutations are also found in Delta, this is not Delta,” Dr. Fauci said. “These mutations have been associated with increased transmissibility and immune evasion.”
Omicron is the fifth designated COVID-19 variant of concern.
Detected first in South Africa, Omicron has been found in 20 countries so far. There are no known cases yet in the United States, but it has been detected in Canada.
Omicron has more than 30 mutations to the spike protein, the part of the virus that binds to human cells, Dr. Fauci said.
Cross-protection from boosters
Though the mutations suggest there is increased transmission of this variant, he said it is too soon to know how this compares to the Delta variant. And although the vaccines may not be as effective against Omicron, Dr. Fauci said there will likely be some protection.
“Remember, as with other variants, although partial immune escape may occur, vaccines, particularly boosters, give a level of antibodies that even with variants like Delta give you a degree of cross-protection, particularly against severe disease,” he said.
“When we say that although these mutations suggest a diminution of protection and a degree of immune evasion, we still, from experience with Delta, can make a reasonable conclusion that you would not eliminate all protection against this particular variant,” Dr. Fauci said.
So far, there is no reason to believe Omicron will cause more severe illness than other variants of concern.
“Although some preliminary information from South Africa suggests no unusual symptoms associated with variant, we do not know, and it is too early to tell,” Dr. Fauci said.
He recommended that people continue to wear masks, wash hands, and avoid crowded indoor venues. Most importantly, he recommended that everyone get their vaccines and boosters.
“One thing has become clear over the last 20 months: We can’t predict the future, but we can be prepared for it,” CDC Director Rochelle P. Walensky, MD, said at the briefing. “We have far more tools to fight the variant today than we did at this time last year.”
A version of this story first appeared on Medscape.com.
The newly detected Omicron COVID-19 variant may be highly infectious and less responsive to available vaccines than other variants, but it is too early to know how it compares to the Delta variant, top infectious disease official Anthony S. Fauci, MD, said Nov. 30.
Dr. Fauci, speaking at a White House COVID-19 briefing, said there’s a “very unusual constellation of changes” across the COVID-19 genome that indicates it is unlike any variant we have seen so far.
“This mutational profile is very different from other variants of interest and concern, and although some mutations are also found in Delta, this is not Delta,” Dr. Fauci said. “These mutations have been associated with increased transmissibility and immune evasion.”
Omicron is the fifth designated COVID-19 variant of concern.
Detected first in South Africa, Omicron has been found in 20 countries so far. There are no known cases yet in the United States, but it has been detected in Canada.
Omicron has more than 30 mutations to the spike protein, the part of the virus that binds to human cells, Dr. Fauci said.
Cross-protection from boosters
Though the mutations suggest there is increased transmission of this variant, he said it is too soon to know how this compares to the Delta variant. And although the vaccines may not be as effective against Omicron, Dr. Fauci said there will likely be some protection.
“Remember, as with other variants, although partial immune escape may occur, vaccines, particularly boosters, give a level of antibodies that even with variants like Delta give you a degree of cross-protection, particularly against severe disease,” he said.
“When we say that although these mutations suggest a diminution of protection and a degree of immune evasion, we still, from experience with Delta, can make a reasonable conclusion that you would not eliminate all protection against this particular variant,” Dr. Fauci said.
So far, there is no reason to believe Omicron will cause more severe illness than other variants of concern.
“Although some preliminary information from South Africa suggests no unusual symptoms associated with variant, we do not know, and it is too early to tell,” Dr. Fauci said.
He recommended that people continue to wear masks, wash hands, and avoid crowded indoor venues. Most importantly, he recommended that everyone get their vaccines and boosters.
“One thing has become clear over the last 20 months: We can’t predict the future, but we can be prepared for it,” CDC Director Rochelle P. Walensky, MD, said at the briefing. “We have far more tools to fight the variant today than we did at this time last year.”
A version of this story first appeared on Medscape.com.
The newly detected Omicron COVID-19 variant may be highly infectious and less responsive to available vaccines than other variants, but it is too early to know how it compares to the Delta variant, top infectious disease official Anthony S. Fauci, MD, said Nov. 30.
Dr. Fauci, speaking at a White House COVID-19 briefing, said there’s a “very unusual constellation of changes” across the COVID-19 genome that indicates it is unlike any variant we have seen so far.
“This mutational profile is very different from other variants of interest and concern, and although some mutations are also found in Delta, this is not Delta,” Dr. Fauci said. “These mutations have been associated with increased transmissibility and immune evasion.”
Omicron is the fifth designated COVID-19 variant of concern.
Detected first in South Africa, Omicron has been found in 20 countries so far. There are no known cases yet in the United States, but it has been detected in Canada.
Omicron has more than 30 mutations to the spike protein, the part of the virus that binds to human cells, Dr. Fauci said.
Cross-protection from boosters
Though the mutations suggest there is increased transmission of this variant, he said it is too soon to know how this compares to the Delta variant. And although the vaccines may not be as effective against Omicron, Dr. Fauci said there will likely be some protection.
“Remember, as with other variants, although partial immune escape may occur, vaccines, particularly boosters, give a level of antibodies that even with variants like Delta give you a degree of cross-protection, particularly against severe disease,” he said.
“When we say that although these mutations suggest a diminution of protection and a degree of immune evasion, we still, from experience with Delta, can make a reasonable conclusion that you would not eliminate all protection against this particular variant,” Dr. Fauci said.
So far, there is no reason to believe Omicron will cause more severe illness than other variants of concern.
“Although some preliminary information from South Africa suggests no unusual symptoms associated with variant, we do not know, and it is too early to tell,” Dr. Fauci said.
He recommended that people continue to wear masks, wash hands, and avoid crowded indoor venues. Most importantly, he recommended that everyone get their vaccines and boosters.
“One thing has become clear over the last 20 months: We can’t predict the future, but we can be prepared for it,” CDC Director Rochelle P. Walensky, MD, said at the briefing. “We have far more tools to fight the variant today than we did at this time last year.”
A version of this story first appeared on Medscape.com.
FDA panel backs first pill for COVID-19 by a small margin
, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.
The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.
The FDA is not bound by the committee’s vote but typically follows its advice.
If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.
The United Kingdom has already authorized the use of Merck’s drug.
“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.
Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.
“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.
Others didn’t agree that the drug should be allowed onto the market.
“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.
Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.
But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.
In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.
On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.
The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.
“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.
“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.
Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.
There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.
Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.
Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.
Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.
Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.
The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.
But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.
Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.
So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.
Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.
“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.
“So we don’t,” Dr. Kartsonis said.
He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.
“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.
Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.
“It was an easy vote for me,” he said.
A version of this article first appeared on Medscape.com.
, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.
The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.
The FDA is not bound by the committee’s vote but typically follows its advice.
If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.
The United Kingdom has already authorized the use of Merck’s drug.
“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.
Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.
“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.
Others didn’t agree that the drug should be allowed onto the market.
“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.
Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.
But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.
In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.
On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.
The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.
“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.
“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.
Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.
There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.
Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.
Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.
Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.
Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.
The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.
But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.
Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.
So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.
Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.
“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.
“So we don’t,” Dr. Kartsonis said.
He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.
“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.
Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.
“It was an easy vote for me,” he said.
A version of this article first appeared on Medscape.com.
, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.
The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.
The FDA is not bound by the committee’s vote but typically follows its advice.
If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.
The United Kingdom has already authorized the use of Merck’s drug.
“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.
Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.
“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.
Others didn’t agree that the drug should be allowed onto the market.
“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.
Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.
But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.
In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.
On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.
The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.
“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.
“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.
Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.
There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.
Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.
Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.
Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.
Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.
The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.
But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.
Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.
So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.
Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.
“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.
“So we don’t,” Dr. Kartsonis said.
He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.
“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.
Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.
“It was an easy vote for me,” he said.
A version of this article first appeared on Medscape.com.