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RSV surge stuns parents and strains providers, but doctors offer help
RSV cases peaked in mid-November, according to the latest Centers for Disease Control and Prevention data, with RSV-associated hospitalizations in the United States among patients 0-4 years having maxed out five times higher than they were at the same time in 2021. These surges strained providers and left parents scrambling for care. Fortunately, pediatric hospitalizations appear to be subsiding.
In interviews, the parents of the child who had a severe case of RSV reflected on their son’s bout with the illness, and doctors described challenges to dealing with the surge in RSV cases this season. The physicians also offered advice on how recognize and respond to future cases of the virus.
Sebastian Witt’s story
“I didn’t even know what RSV was,” said Malte Witt, whose son, Sebastian, 2, was recently hospitalized for RSV in Denver.
Mr. Witt and his wife, Emily Witt, both 32, thought they were dealing with a typical cold until Sebastian’s condition dramatically deteriorated about 36 hours after symptom onset.
“He basically just slumped over and collapsed, coughing uncontrollably,” Mr. Witt said in an interview. “He couldn’t catch his breath.”
The Witts rushed Sebastian to the ED at Children’s Hospital Colorado, expecting to see a doctor immediately. Instead, they spent the night in an overcrowded waiting room alongside many other families in the same situation.
“There was no room for anyone to sit anywhere,” Mr. Witt said. “There were people sitting on the floor. I counted maybe six children hooked up to oxygen when we walked in.”
After waiting approximately 45 minutes, a nurse checked Sebastian’s oxygen saturation. The readings were 79%-83%. This range is significantly below thresholds for supplemental oxygen described by most pediatric guidelines, which range from 90 to 94%.
The nurse connected Sebastian to bottled oxygen in the waiting room, and a recheck 4 hours later showed that his oxygen saturation had improved.
But the improvement didn’t last.
“At roughly hour 10 in the waiting room – it was 4 in the morning – you could tell that Seb was exhausted, really not acting like himself,” Mr. Witt said. “We thought maybe it’s just late at night, he hasn’t really slept. But then Emily noticed that his oxygen tank had run out.”
Mr. Witt told a nurse, and after another check revealed low oxygen saturation, Sebastian was finally admitted.
Early RSV surge strains pediatric providers
With RSV-associated hospitalizations peaking at 48 per 100,000 children, Colorado has been among the states hardest hit by the virus. New Mexico – where hospitalizations peaked at 56.4 per 100,000 children – comes in second. Even in states like California, where hospitalization rates have been almost 10-fold lower than New Mexico, pediatric providers have been stretched to their limits.
“Many hospitals are really being overwhelmed with admissions for RSV, both routine RSV – relatively mild hospitalizations with bronchiolitis – as well as kids in the ICU with more severe cases,” said Dean Blumberg, MD, chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, said in an interview.
Dr. Blumberg believes the severity of the 2022-2023 RSV season is likely COVID related.
“All community-associated respiratory viral infections are out of whack because of the pandemic, and all the masking and social distancing that was occurring,” he said.
This may also explain why older kids are coming down with more severe cases of RSV.
“Some children are getting RSV for the first time as older children,” Dr. Blumberg said, noting that, historically, most children were infected in the first 2 years of life. “There are reports of children 3 or 4 years of age being admitted with their first episode of RSV because of the [COVID] pandemic.”
This year’s RSV season is also notable for arriving early, potentially catching the community off guard, according to Jennifer D. Kusma, MD, a primary care pediatrician at Ann & Robert H. Lurie Children’s Hospital of Chicago.
“People who should have been protected often weren’t protected yet,” Dr. Kusma said in an interview.
Treatments new, old, and unproven
On Nov. 17, in the midst of the RSV surge, the American Academy of Pediatrics issued updated guidance for palivizumab, an RSV-targeting monoclonal antibody labeled for children at risk of severe RSV, including those with pre-existing lung or heart conditions, and infants with a history of premature birth (less than or equal to 35 weeks’ gestational age).
“If RSV disease activity persists at high levels in a given region through the fall and winter, the AAP supports providing more than five consecutive doses of palivizumab to eligible children,” the update stated.
Insurance companies appear to be responding in kind, covering additional doses for children in need.
“[Payers] have agreed that, if [palivizumab] needs to be given for an additional month or 2 or 3, then they’re making a commitment that they’ll reimburse hospitals for providing that,” Dr. Blumberg said.
For ineligible patients, such as Sebastian, who was born prematurely at 36 weeks – 1 week shy of the label requirement – treatment relies upon supportive care with oxygen and IV fluids.
At home, parents are left with simpler options.
Dr. Blumberg and Dr. Kusma recommended keeping children hydrated, maintaining humidified air, and using saline nose drops with bulb suction to clear mucus.
In the Witts’ experience, that last step may be easier said than done.
“Every time a nurse would walk into the room, Sebastian would yell: ‘Go away, doctor! I don’t want snot sucker!’” Mr. Witt said.
“If you over snot-suck, that’s really uncomfortable for the kid, and really hard for you,” Ms. Witt said. “And it doesn’t make much of a difference. It’s just very hard to find a middle ground, where you’re helping and keeping them comfortable.”
Some parents are turning to novel strategies, such as nebulized hypertonic saline, currently marketed on Amazon for children with RSV.
Although the AAP offers a weak recommendation for nebulized hypertonic saline in children hospitalized more than 72 hours, they advise against it in the emergency setting, citing inconsistent findings in clinical trials.
To any parents tempted by thousands of positive Amazon reviews, Dr. Blumberg said, “I wouldn’t waste my money on that.”
Dr. Kusma agreed.
“[Nebulized hypertonic saline] can be irritating,” she said. “It’s saltwater, essentially. If a parent is in the position where they’re worried about their child’s breathing to the point that they think they need to use it, I would err on the side of calling your pediatrician and being seen.”
Going in, coming home
Dr. Kusma said parents should seek medical attention if a child is breathing faster and working harder to get air. Increased work of breathing is characterized by pulling of the skin at the notch where the throat meets the chest bone (tracheal tugging), and flattening of the belly that makes the ribcage more prominent.
Mr. Witt saw these signs in Sebastian. He knew they were significant, because a friend who is a nurse had previously shown him some examples of children who exhibited these symptoms online.
“That’s how I knew that things were actually really dangerous,” Mr. Witt said. “Had she not shown me those videos a month and a half before this happened, I don’t know that we would have hit the alarm bell as quickly as we did.”
After spending their second night and the following day in a cramped preoperative room converted to manage overflow from the emergency department, Sebastian’s condition improved, and he was discharged. The Witts are relieved to be home, but frustrations from their ordeal remain, especially considering the estimated $5,000 in out-of-pocket costs they expect to pay.
“How is this our health care system?” Ms. Witt asked. “This is unbelievable.”
An optimistic outlook
RSV seasons typically demonstrate a clear peak, followed by a decline through the rest of the season, suggesting better times lie ahead; however, this season has been anything but typical.
“I’m hopeful that it will just go away and stay away,” Dr. Kusma said, citing this trend. “But I can’t know for sure.”
To anxious parents, Dr. Blumberg offered an optimistic view of RSV seasons to come.
“There’s hope,” he said. “There are vaccines that are being developed that are very close to FDA approval. So, it’s possible that this time next year, we might have widespread RSV vaccination available for children so that we don’t have to go through this nightmare again.”
Dr. Blumberg and Dr. Kusma disclosed no relevant conflicts of interest.
RSV cases peaked in mid-November, according to the latest Centers for Disease Control and Prevention data, with RSV-associated hospitalizations in the United States among patients 0-4 years having maxed out five times higher than they were at the same time in 2021. These surges strained providers and left parents scrambling for care. Fortunately, pediatric hospitalizations appear to be subsiding.
In interviews, the parents of the child who had a severe case of RSV reflected on their son’s bout with the illness, and doctors described challenges to dealing with the surge in RSV cases this season. The physicians also offered advice on how recognize and respond to future cases of the virus.
Sebastian Witt’s story
“I didn’t even know what RSV was,” said Malte Witt, whose son, Sebastian, 2, was recently hospitalized for RSV in Denver.
Mr. Witt and his wife, Emily Witt, both 32, thought they were dealing with a typical cold until Sebastian’s condition dramatically deteriorated about 36 hours after symptom onset.
“He basically just slumped over and collapsed, coughing uncontrollably,” Mr. Witt said in an interview. “He couldn’t catch his breath.”
The Witts rushed Sebastian to the ED at Children’s Hospital Colorado, expecting to see a doctor immediately. Instead, they spent the night in an overcrowded waiting room alongside many other families in the same situation.
“There was no room for anyone to sit anywhere,” Mr. Witt said. “There were people sitting on the floor. I counted maybe six children hooked up to oxygen when we walked in.”
After waiting approximately 45 minutes, a nurse checked Sebastian’s oxygen saturation. The readings were 79%-83%. This range is significantly below thresholds for supplemental oxygen described by most pediatric guidelines, which range from 90 to 94%.
The nurse connected Sebastian to bottled oxygen in the waiting room, and a recheck 4 hours later showed that his oxygen saturation had improved.
But the improvement didn’t last.
“At roughly hour 10 in the waiting room – it was 4 in the morning – you could tell that Seb was exhausted, really not acting like himself,” Mr. Witt said. “We thought maybe it’s just late at night, he hasn’t really slept. But then Emily noticed that his oxygen tank had run out.”
Mr. Witt told a nurse, and after another check revealed low oxygen saturation, Sebastian was finally admitted.
Early RSV surge strains pediatric providers
With RSV-associated hospitalizations peaking at 48 per 100,000 children, Colorado has been among the states hardest hit by the virus. New Mexico – where hospitalizations peaked at 56.4 per 100,000 children – comes in second. Even in states like California, where hospitalization rates have been almost 10-fold lower than New Mexico, pediatric providers have been stretched to their limits.
“Many hospitals are really being overwhelmed with admissions for RSV, both routine RSV – relatively mild hospitalizations with bronchiolitis – as well as kids in the ICU with more severe cases,” said Dean Blumberg, MD, chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, said in an interview.
Dr. Blumberg believes the severity of the 2022-2023 RSV season is likely COVID related.
“All community-associated respiratory viral infections are out of whack because of the pandemic, and all the masking and social distancing that was occurring,” he said.
This may also explain why older kids are coming down with more severe cases of RSV.
“Some children are getting RSV for the first time as older children,” Dr. Blumberg said, noting that, historically, most children were infected in the first 2 years of life. “There are reports of children 3 or 4 years of age being admitted with their first episode of RSV because of the [COVID] pandemic.”
This year’s RSV season is also notable for arriving early, potentially catching the community off guard, according to Jennifer D. Kusma, MD, a primary care pediatrician at Ann & Robert H. Lurie Children’s Hospital of Chicago.
“People who should have been protected often weren’t protected yet,” Dr. Kusma said in an interview.
Treatments new, old, and unproven
On Nov. 17, in the midst of the RSV surge, the American Academy of Pediatrics issued updated guidance for palivizumab, an RSV-targeting monoclonal antibody labeled for children at risk of severe RSV, including those with pre-existing lung or heart conditions, and infants with a history of premature birth (less than or equal to 35 weeks’ gestational age).
“If RSV disease activity persists at high levels in a given region through the fall and winter, the AAP supports providing more than five consecutive doses of palivizumab to eligible children,” the update stated.
Insurance companies appear to be responding in kind, covering additional doses for children in need.
“[Payers] have agreed that, if [palivizumab] needs to be given for an additional month or 2 or 3, then they’re making a commitment that they’ll reimburse hospitals for providing that,” Dr. Blumberg said.
For ineligible patients, such as Sebastian, who was born prematurely at 36 weeks – 1 week shy of the label requirement – treatment relies upon supportive care with oxygen and IV fluids.
At home, parents are left with simpler options.
Dr. Blumberg and Dr. Kusma recommended keeping children hydrated, maintaining humidified air, and using saline nose drops with bulb suction to clear mucus.
In the Witts’ experience, that last step may be easier said than done.
“Every time a nurse would walk into the room, Sebastian would yell: ‘Go away, doctor! I don’t want snot sucker!’” Mr. Witt said.
“If you over snot-suck, that’s really uncomfortable for the kid, and really hard for you,” Ms. Witt said. “And it doesn’t make much of a difference. It’s just very hard to find a middle ground, where you’re helping and keeping them comfortable.”
Some parents are turning to novel strategies, such as nebulized hypertonic saline, currently marketed on Amazon for children with RSV.
Although the AAP offers a weak recommendation for nebulized hypertonic saline in children hospitalized more than 72 hours, they advise against it in the emergency setting, citing inconsistent findings in clinical trials.
To any parents tempted by thousands of positive Amazon reviews, Dr. Blumberg said, “I wouldn’t waste my money on that.”
Dr. Kusma agreed.
“[Nebulized hypertonic saline] can be irritating,” she said. “It’s saltwater, essentially. If a parent is in the position where they’re worried about their child’s breathing to the point that they think they need to use it, I would err on the side of calling your pediatrician and being seen.”
Going in, coming home
Dr. Kusma said parents should seek medical attention if a child is breathing faster and working harder to get air. Increased work of breathing is characterized by pulling of the skin at the notch where the throat meets the chest bone (tracheal tugging), and flattening of the belly that makes the ribcage more prominent.
Mr. Witt saw these signs in Sebastian. He knew they were significant, because a friend who is a nurse had previously shown him some examples of children who exhibited these symptoms online.
“That’s how I knew that things were actually really dangerous,” Mr. Witt said. “Had she not shown me those videos a month and a half before this happened, I don’t know that we would have hit the alarm bell as quickly as we did.”
After spending their second night and the following day in a cramped preoperative room converted to manage overflow from the emergency department, Sebastian’s condition improved, and he was discharged. The Witts are relieved to be home, but frustrations from their ordeal remain, especially considering the estimated $5,000 in out-of-pocket costs they expect to pay.
“How is this our health care system?” Ms. Witt asked. “This is unbelievable.”
An optimistic outlook
RSV seasons typically demonstrate a clear peak, followed by a decline through the rest of the season, suggesting better times lie ahead; however, this season has been anything but typical.
“I’m hopeful that it will just go away and stay away,” Dr. Kusma said, citing this trend. “But I can’t know for sure.”
To anxious parents, Dr. Blumberg offered an optimistic view of RSV seasons to come.
“There’s hope,” he said. “There are vaccines that are being developed that are very close to FDA approval. So, it’s possible that this time next year, we might have widespread RSV vaccination available for children so that we don’t have to go through this nightmare again.”
Dr. Blumberg and Dr. Kusma disclosed no relevant conflicts of interest.
RSV cases peaked in mid-November, according to the latest Centers for Disease Control and Prevention data, with RSV-associated hospitalizations in the United States among patients 0-4 years having maxed out five times higher than they were at the same time in 2021. These surges strained providers and left parents scrambling for care. Fortunately, pediatric hospitalizations appear to be subsiding.
In interviews, the parents of the child who had a severe case of RSV reflected on their son’s bout with the illness, and doctors described challenges to dealing with the surge in RSV cases this season. The physicians also offered advice on how recognize and respond to future cases of the virus.
Sebastian Witt’s story
“I didn’t even know what RSV was,” said Malte Witt, whose son, Sebastian, 2, was recently hospitalized for RSV in Denver.
Mr. Witt and his wife, Emily Witt, both 32, thought they were dealing with a typical cold until Sebastian’s condition dramatically deteriorated about 36 hours after symptom onset.
“He basically just slumped over and collapsed, coughing uncontrollably,” Mr. Witt said in an interview. “He couldn’t catch his breath.”
The Witts rushed Sebastian to the ED at Children’s Hospital Colorado, expecting to see a doctor immediately. Instead, they spent the night in an overcrowded waiting room alongside many other families in the same situation.
“There was no room for anyone to sit anywhere,” Mr. Witt said. “There were people sitting on the floor. I counted maybe six children hooked up to oxygen when we walked in.”
After waiting approximately 45 minutes, a nurse checked Sebastian’s oxygen saturation. The readings were 79%-83%. This range is significantly below thresholds for supplemental oxygen described by most pediatric guidelines, which range from 90 to 94%.
The nurse connected Sebastian to bottled oxygen in the waiting room, and a recheck 4 hours later showed that his oxygen saturation had improved.
But the improvement didn’t last.
“At roughly hour 10 in the waiting room – it was 4 in the morning – you could tell that Seb was exhausted, really not acting like himself,” Mr. Witt said. “We thought maybe it’s just late at night, he hasn’t really slept. But then Emily noticed that his oxygen tank had run out.”
Mr. Witt told a nurse, and after another check revealed low oxygen saturation, Sebastian was finally admitted.
Early RSV surge strains pediatric providers
With RSV-associated hospitalizations peaking at 48 per 100,000 children, Colorado has been among the states hardest hit by the virus. New Mexico – where hospitalizations peaked at 56.4 per 100,000 children – comes in second. Even in states like California, where hospitalization rates have been almost 10-fold lower than New Mexico, pediatric providers have been stretched to their limits.
“Many hospitals are really being overwhelmed with admissions for RSV, both routine RSV – relatively mild hospitalizations with bronchiolitis – as well as kids in the ICU with more severe cases,” said Dean Blumberg, MD, chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, said in an interview.
Dr. Blumberg believes the severity of the 2022-2023 RSV season is likely COVID related.
“All community-associated respiratory viral infections are out of whack because of the pandemic, and all the masking and social distancing that was occurring,” he said.
This may also explain why older kids are coming down with more severe cases of RSV.
“Some children are getting RSV for the first time as older children,” Dr. Blumberg said, noting that, historically, most children were infected in the first 2 years of life. “There are reports of children 3 or 4 years of age being admitted with their first episode of RSV because of the [COVID] pandemic.”
This year’s RSV season is also notable for arriving early, potentially catching the community off guard, according to Jennifer D. Kusma, MD, a primary care pediatrician at Ann & Robert H. Lurie Children’s Hospital of Chicago.
“People who should have been protected often weren’t protected yet,” Dr. Kusma said in an interview.
Treatments new, old, and unproven
On Nov. 17, in the midst of the RSV surge, the American Academy of Pediatrics issued updated guidance for palivizumab, an RSV-targeting monoclonal antibody labeled for children at risk of severe RSV, including those with pre-existing lung or heart conditions, and infants with a history of premature birth (less than or equal to 35 weeks’ gestational age).
“If RSV disease activity persists at high levels in a given region through the fall and winter, the AAP supports providing more than five consecutive doses of palivizumab to eligible children,” the update stated.
Insurance companies appear to be responding in kind, covering additional doses for children in need.
“[Payers] have agreed that, if [palivizumab] needs to be given for an additional month or 2 or 3, then they’re making a commitment that they’ll reimburse hospitals for providing that,” Dr. Blumberg said.
For ineligible patients, such as Sebastian, who was born prematurely at 36 weeks – 1 week shy of the label requirement – treatment relies upon supportive care with oxygen and IV fluids.
At home, parents are left with simpler options.
Dr. Blumberg and Dr. Kusma recommended keeping children hydrated, maintaining humidified air, and using saline nose drops with bulb suction to clear mucus.
In the Witts’ experience, that last step may be easier said than done.
“Every time a nurse would walk into the room, Sebastian would yell: ‘Go away, doctor! I don’t want snot sucker!’” Mr. Witt said.
“If you over snot-suck, that’s really uncomfortable for the kid, and really hard for you,” Ms. Witt said. “And it doesn’t make much of a difference. It’s just very hard to find a middle ground, where you’re helping and keeping them comfortable.”
Some parents are turning to novel strategies, such as nebulized hypertonic saline, currently marketed on Amazon for children with RSV.
Although the AAP offers a weak recommendation for nebulized hypertonic saline in children hospitalized more than 72 hours, they advise against it in the emergency setting, citing inconsistent findings in clinical trials.
To any parents tempted by thousands of positive Amazon reviews, Dr. Blumberg said, “I wouldn’t waste my money on that.”
Dr. Kusma agreed.
“[Nebulized hypertonic saline] can be irritating,” she said. “It’s saltwater, essentially. If a parent is in the position where they’re worried about their child’s breathing to the point that they think they need to use it, I would err on the side of calling your pediatrician and being seen.”
Going in, coming home
Dr. Kusma said parents should seek medical attention if a child is breathing faster and working harder to get air. Increased work of breathing is characterized by pulling of the skin at the notch where the throat meets the chest bone (tracheal tugging), and flattening of the belly that makes the ribcage more prominent.
Mr. Witt saw these signs in Sebastian. He knew they were significant, because a friend who is a nurse had previously shown him some examples of children who exhibited these symptoms online.
“That’s how I knew that things were actually really dangerous,” Mr. Witt said. “Had she not shown me those videos a month and a half before this happened, I don’t know that we would have hit the alarm bell as quickly as we did.”
After spending their second night and the following day in a cramped preoperative room converted to manage overflow from the emergency department, Sebastian’s condition improved, and he was discharged. The Witts are relieved to be home, but frustrations from their ordeal remain, especially considering the estimated $5,000 in out-of-pocket costs they expect to pay.
“How is this our health care system?” Ms. Witt asked. “This is unbelievable.”
An optimistic outlook
RSV seasons typically demonstrate a clear peak, followed by a decline through the rest of the season, suggesting better times lie ahead; however, this season has been anything but typical.
“I’m hopeful that it will just go away and stay away,” Dr. Kusma said, citing this trend. “But I can’t know for sure.”
To anxious parents, Dr. Blumberg offered an optimistic view of RSV seasons to come.
“There’s hope,” he said. “There are vaccines that are being developed that are very close to FDA approval. So, it’s possible that this time next year, we might have widespread RSV vaccination available for children so that we don’t have to go through this nightmare again.”
Dr. Blumberg and Dr. Kusma disclosed no relevant conflicts of interest.
Watching violent TV in preschool linked with emotional, behavioral issues at age 12
Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.
These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.
Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.
Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.
At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.
To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.
Dr. Pagani noted that these were not “garden-variety” statistical techniques.
“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”
She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.
For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.
“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
Seeing TV through a child’s eyes
According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.
“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”
Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.
Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.
“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”
She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.
“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
Choosing quality time over screen time
Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.
There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.
If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.
“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”
In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.
“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”
Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.
“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”
Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.
The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.
Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.
These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.
Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.
Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.
At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.
To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.
Dr. Pagani noted that these were not “garden-variety” statistical techniques.
“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”
She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.
For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.
“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
Seeing TV through a child’s eyes
According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.
“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”
Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.
Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.
“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”
She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.
“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
Choosing quality time over screen time
Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.
There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.
If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.
“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”
In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.
“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”
Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.
“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”
Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.
The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.
Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.
These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.
Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.
Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.
At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.
To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.
Dr. Pagani noted that these were not “garden-variety” statistical techniques.
“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”
She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.
For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.
“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
Seeing TV through a child’s eyes
According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.
“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”
Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.
Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.
“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”
She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.
“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
Choosing quality time over screen time
Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.
There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.
If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.
“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”
In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.
“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”
Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.
“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”
Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.
The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.
FROM THE JOURNAL OF DEVELOPMENTAL & BEHAVIORAL PEDIATRICS
Machine learning identifies childhood characteristics that predict bipolar disorder
This is the first quantitative approach to predict bipolar disorder, offering sensitivity and specificity of 75% and 76%, respectively, reported lead author Mai Uchida, MD, director of the pediatric depression program at Massachusetts General Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, and colleagues. With further development, the model could be used to identify at-risk children via electronic medical records, enabling earlier monitoring and intervention.
“Although longitudinal studies have found the prognosis of early-onset mood disorders to be unfavorable, research has also shown there are effective treatments and therapies that could significantly alleviate the patients’ and their families’ struggles from the diagnoses,” the investigators wrote in the Journal of Psychiatric Research. “Thus, early identification of the risks and interventions for early symptoms of pediatric mood disorders is crucial.”
To this end, Dr. Uchida and colleagues teamed up with the Gabrieli Lab at MIT, who have published extensively in the realm of neurodevelopment. They sourced data from 492 children, 6-18 years at baseline, who were involved in two longitudinal case-control family studies focused on ADHD. Inputs included psychometric scales, structured diagnostic interviews, social and cognitive functioning assessments, and sociodemographic data.
At 10-year follow-up, 10% of these children had developed bipolar disorder, a notably higher rate than the 3%-4% prevalence in the general population.
“This is a population that’s overrepresented,” Dr. Uchida said in an interview.
She offered two primary reasons for this: First, the families involved in the study were probably willing to be followed for 10 years because they had ongoing concerns about their child’s mental health. Second, the studies enrolled children diagnosed with ADHD, a condition associated with increased risk of bipolar disorder.
Using machine learning algorithms that processed the baseline data while accounting for the skewed distribution, the investigators were able to predict which of the children in the population would go on to develop bipolar disorder. The final model offered a sensitivity of 75%, a specificity of 76%, and an area under the receiver operating characteristic curve of 75%.
“To the best of our knowledge, this represents the first study using machine-learning algorithms for this purpose in pediatric psychiatry,” the investigators wrote.
Integrating models into electronic medical records
In the future, this model, or one like it, could be incorporated into software that automatically analyzes electronic medical records and notifies physicians about high-risk patients, Dr. Uchida predicted.
“Not all patients would connect to intervention,” she said. “Maybe it just means that you invite them in for a visit, or you observe them a little bit more carefully. I think that’s where we are hoping that machine learning and medical practice will go.”
When asked about the potential bias posed by psychiatric evaluation, compared with something like blood work results, Dr. Uchida suggested that this subjectivity can be overcome.
“I’m not entirely bothered by that,” she said, offering a list of objective data points that could be harvested from records, such as number of referrals, medications, and hospitalizations. Narrative text in medical records could also be analyzed, she said, potentially detecting key words that are more often associated with high-risk patients.
“Risk prediction is never going to be 100% accurate,” Dr. Uchida said. “But I do think that there will be things [in electronic medical records] that could guide how worried we should be, or how quickly we should intervene.”
Opening doors to personalized care
Martin Gignac, MD, chief of psychiatry at Montreal Children’s Hospital and associate professor at McGill University, Montreal, said the present study offers further support for the existence of pediatric-onset bipolar disorder, which “remains controversial” despite “solid evidence.”
“I’m impressed that we have 10-year-long longitudinal follow-up studies that corroborate the importance of this disorder, and show strong predictors of who is at risk,” Dr. Gignac said in an interview. “Clinicians treating a pediatric population should be aware that some of those children with mental health problems might have severe mental health problems, and you have to have the appropriate tools to screen them.”
Advanced tools like the one developed by Dr. Uchida and colleagues should lead to more personalized care, he said.
“We’re going to be able to define what your individual risk is, and maybe most importantly, what you can do to prevent the development of certain disorders,” Dr. Gignac said. “Are there any risks that are dynamic in nature, and that we can act upon? Exposure to stress, for example.”
While more work is needed to bring machine learning into daily psychiatric practice, Dr. Gignac concluded on an optimistic note.
“These instruments should translate from research into clinical practice in order to make difference for the patients we care for,” he said. “This is the type of hope that I hold – that it’s going to be applicable in clinical practice, hopefully, in the near future.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Gignac disclosed no relevant competing interests.
This is the first quantitative approach to predict bipolar disorder, offering sensitivity and specificity of 75% and 76%, respectively, reported lead author Mai Uchida, MD, director of the pediatric depression program at Massachusetts General Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, and colleagues. With further development, the model could be used to identify at-risk children via electronic medical records, enabling earlier monitoring and intervention.
“Although longitudinal studies have found the prognosis of early-onset mood disorders to be unfavorable, research has also shown there are effective treatments and therapies that could significantly alleviate the patients’ and their families’ struggles from the diagnoses,” the investigators wrote in the Journal of Psychiatric Research. “Thus, early identification of the risks and interventions for early symptoms of pediatric mood disorders is crucial.”
To this end, Dr. Uchida and colleagues teamed up with the Gabrieli Lab at MIT, who have published extensively in the realm of neurodevelopment. They sourced data from 492 children, 6-18 years at baseline, who were involved in two longitudinal case-control family studies focused on ADHD. Inputs included psychometric scales, structured diagnostic interviews, social and cognitive functioning assessments, and sociodemographic data.
At 10-year follow-up, 10% of these children had developed bipolar disorder, a notably higher rate than the 3%-4% prevalence in the general population.
“This is a population that’s overrepresented,” Dr. Uchida said in an interview.
She offered two primary reasons for this: First, the families involved in the study were probably willing to be followed for 10 years because they had ongoing concerns about their child’s mental health. Second, the studies enrolled children diagnosed with ADHD, a condition associated with increased risk of bipolar disorder.
Using machine learning algorithms that processed the baseline data while accounting for the skewed distribution, the investigators were able to predict which of the children in the population would go on to develop bipolar disorder. The final model offered a sensitivity of 75%, a specificity of 76%, and an area under the receiver operating characteristic curve of 75%.
“To the best of our knowledge, this represents the first study using machine-learning algorithms for this purpose in pediatric psychiatry,” the investigators wrote.
Integrating models into electronic medical records
In the future, this model, or one like it, could be incorporated into software that automatically analyzes electronic medical records and notifies physicians about high-risk patients, Dr. Uchida predicted.
“Not all patients would connect to intervention,” she said. “Maybe it just means that you invite them in for a visit, or you observe them a little bit more carefully. I think that’s where we are hoping that machine learning and medical practice will go.”
When asked about the potential bias posed by psychiatric evaluation, compared with something like blood work results, Dr. Uchida suggested that this subjectivity can be overcome.
“I’m not entirely bothered by that,” she said, offering a list of objective data points that could be harvested from records, such as number of referrals, medications, and hospitalizations. Narrative text in medical records could also be analyzed, she said, potentially detecting key words that are more often associated with high-risk patients.
“Risk prediction is never going to be 100% accurate,” Dr. Uchida said. “But I do think that there will be things [in electronic medical records] that could guide how worried we should be, or how quickly we should intervene.”
Opening doors to personalized care
Martin Gignac, MD, chief of psychiatry at Montreal Children’s Hospital and associate professor at McGill University, Montreal, said the present study offers further support for the existence of pediatric-onset bipolar disorder, which “remains controversial” despite “solid evidence.”
“I’m impressed that we have 10-year-long longitudinal follow-up studies that corroborate the importance of this disorder, and show strong predictors of who is at risk,” Dr. Gignac said in an interview. “Clinicians treating a pediatric population should be aware that some of those children with mental health problems might have severe mental health problems, and you have to have the appropriate tools to screen them.”
Advanced tools like the one developed by Dr. Uchida and colleagues should lead to more personalized care, he said.
“We’re going to be able to define what your individual risk is, and maybe most importantly, what you can do to prevent the development of certain disorders,” Dr. Gignac said. “Are there any risks that are dynamic in nature, and that we can act upon? Exposure to stress, for example.”
While more work is needed to bring machine learning into daily psychiatric practice, Dr. Gignac concluded on an optimistic note.
“These instruments should translate from research into clinical practice in order to make difference for the patients we care for,” he said. “This is the type of hope that I hold – that it’s going to be applicable in clinical practice, hopefully, in the near future.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Gignac disclosed no relevant competing interests.
This is the first quantitative approach to predict bipolar disorder, offering sensitivity and specificity of 75% and 76%, respectively, reported lead author Mai Uchida, MD, director of the pediatric depression program at Massachusetts General Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, and colleagues. With further development, the model could be used to identify at-risk children via electronic medical records, enabling earlier monitoring and intervention.
“Although longitudinal studies have found the prognosis of early-onset mood disorders to be unfavorable, research has also shown there are effective treatments and therapies that could significantly alleviate the patients’ and their families’ struggles from the diagnoses,” the investigators wrote in the Journal of Psychiatric Research. “Thus, early identification of the risks and interventions for early symptoms of pediatric mood disorders is crucial.”
To this end, Dr. Uchida and colleagues teamed up with the Gabrieli Lab at MIT, who have published extensively in the realm of neurodevelopment. They sourced data from 492 children, 6-18 years at baseline, who were involved in two longitudinal case-control family studies focused on ADHD. Inputs included psychometric scales, structured diagnostic interviews, social and cognitive functioning assessments, and sociodemographic data.
At 10-year follow-up, 10% of these children had developed bipolar disorder, a notably higher rate than the 3%-4% prevalence in the general population.
“This is a population that’s overrepresented,” Dr. Uchida said in an interview.
She offered two primary reasons for this: First, the families involved in the study were probably willing to be followed for 10 years because they had ongoing concerns about their child’s mental health. Second, the studies enrolled children diagnosed with ADHD, a condition associated with increased risk of bipolar disorder.
Using machine learning algorithms that processed the baseline data while accounting for the skewed distribution, the investigators were able to predict which of the children in the population would go on to develop bipolar disorder. The final model offered a sensitivity of 75%, a specificity of 76%, and an area under the receiver operating characteristic curve of 75%.
“To the best of our knowledge, this represents the first study using machine-learning algorithms for this purpose in pediatric psychiatry,” the investigators wrote.
Integrating models into electronic medical records
In the future, this model, or one like it, could be incorporated into software that automatically analyzes electronic medical records and notifies physicians about high-risk patients, Dr. Uchida predicted.
“Not all patients would connect to intervention,” she said. “Maybe it just means that you invite them in for a visit, or you observe them a little bit more carefully. I think that’s where we are hoping that machine learning and medical practice will go.”
When asked about the potential bias posed by psychiatric evaluation, compared with something like blood work results, Dr. Uchida suggested that this subjectivity can be overcome.
“I’m not entirely bothered by that,” she said, offering a list of objective data points that could be harvested from records, such as number of referrals, medications, and hospitalizations. Narrative text in medical records could also be analyzed, she said, potentially detecting key words that are more often associated with high-risk patients.
“Risk prediction is never going to be 100% accurate,” Dr. Uchida said. “But I do think that there will be things [in electronic medical records] that could guide how worried we should be, or how quickly we should intervene.”
Opening doors to personalized care
Martin Gignac, MD, chief of psychiatry at Montreal Children’s Hospital and associate professor at McGill University, Montreal, said the present study offers further support for the existence of pediatric-onset bipolar disorder, which “remains controversial” despite “solid evidence.”
“I’m impressed that we have 10-year-long longitudinal follow-up studies that corroborate the importance of this disorder, and show strong predictors of who is at risk,” Dr. Gignac said in an interview. “Clinicians treating a pediatric population should be aware that some of those children with mental health problems might have severe mental health problems, and you have to have the appropriate tools to screen them.”
Advanced tools like the one developed by Dr. Uchida and colleagues should lead to more personalized care, he said.
“We’re going to be able to define what your individual risk is, and maybe most importantly, what you can do to prevent the development of certain disorders,” Dr. Gignac said. “Are there any risks that are dynamic in nature, and that we can act upon? Exposure to stress, for example.”
While more work is needed to bring machine learning into daily psychiatric practice, Dr. Gignac concluded on an optimistic note.
“These instruments should translate from research into clinical practice in order to make difference for the patients we care for,” he said. “This is the type of hope that I hold – that it’s going to be applicable in clinical practice, hopefully, in the near future.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Gignac disclosed no relevant competing interests.
FROM THE JOURNAL OF PSYCHIATRIC RESEARCH
Sex-linked IL-22 activity may affect NAFLD outcomes
Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.
These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.
“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”
Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.
To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
Human data
To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.
“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
Mouse data
Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.
Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.
“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”
In the meantime, the present data may steer drug development.
“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.
The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.
The cytokine interleukin-22 has potential as a therapeutic for nonalcoholic fatty liver disease, as it has been shown to decrease fat accumulation in hepatocytes and has various other liver protective effects such as prevention of cell death, enhancement of proliferation, and, importantly, reduction of liver fibrosis progression. Indeed, a recombinant derivative of IL22 has been studied in a clinical trial of alcoholic liver disease and has been found to be safe. However, the beneficial effect of this cytokine is context dependent. High levels of IL22 increased inflammation or fibrosis in hepatitis B infection and in toxic injury models in mouse models.
This is in line with observations that progression to cirrhosis in NAFLD is greater after menopause. On the other hand, women are more likely to develop cirrhosis than men despite higher levels of IL22, indicating more factors are at play in the progression of NAFLD. Overall, this report should alert investigators to consider the sex-specific effects of emerging therapies for NAFLD. Future IL22-based trials must include sex-based subgroup analyses.
Kirk Wangensteen, MD, PhD, is with the department of medicine, division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. He declares no relevant conflicts of interest.
The cytokine interleukin-22 has potential as a therapeutic for nonalcoholic fatty liver disease, as it has been shown to decrease fat accumulation in hepatocytes and has various other liver protective effects such as prevention of cell death, enhancement of proliferation, and, importantly, reduction of liver fibrosis progression. Indeed, a recombinant derivative of IL22 has been studied in a clinical trial of alcoholic liver disease and has been found to be safe. However, the beneficial effect of this cytokine is context dependent. High levels of IL22 increased inflammation or fibrosis in hepatitis B infection and in toxic injury models in mouse models.
This is in line with observations that progression to cirrhosis in NAFLD is greater after menopause. On the other hand, women are more likely to develop cirrhosis than men despite higher levels of IL22, indicating more factors are at play in the progression of NAFLD. Overall, this report should alert investigators to consider the sex-specific effects of emerging therapies for NAFLD. Future IL22-based trials must include sex-based subgroup analyses.
Kirk Wangensteen, MD, PhD, is with the department of medicine, division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. He declares no relevant conflicts of interest.
The cytokine interleukin-22 has potential as a therapeutic for nonalcoholic fatty liver disease, as it has been shown to decrease fat accumulation in hepatocytes and has various other liver protective effects such as prevention of cell death, enhancement of proliferation, and, importantly, reduction of liver fibrosis progression. Indeed, a recombinant derivative of IL22 has been studied in a clinical trial of alcoholic liver disease and has been found to be safe. However, the beneficial effect of this cytokine is context dependent. High levels of IL22 increased inflammation or fibrosis in hepatitis B infection and in toxic injury models in mouse models.
This is in line with observations that progression to cirrhosis in NAFLD is greater after menopause. On the other hand, women are more likely to develop cirrhosis than men despite higher levels of IL22, indicating more factors are at play in the progression of NAFLD. Overall, this report should alert investigators to consider the sex-specific effects of emerging therapies for NAFLD. Future IL22-based trials must include sex-based subgroup analyses.
Kirk Wangensteen, MD, PhD, is with the department of medicine, division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. He declares no relevant conflicts of interest.
Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.
These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.
“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”
Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.
To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
Human data
To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.
“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
Mouse data
Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.
Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.
“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”
In the meantime, the present data may steer drug development.
“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.
The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.
Interleukin-22 may mitigate nonalcoholic fatty liver disease (NAFLD)–related fibrosis in females but not males, suggesting a sex-linked hepatoprotective pathway, according to investigators.
These differences between men and women should be considered when conducting clinical trials for IL-22–targeting therapies, reported lead author Mohamed N. Abdelnabi, MSc, of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and colleagues.
“IL-22 is a pleiotropic cytokine with both inflammatory and protective effects during injury and repair in various tissues including the liver,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, noting that IL-22 activity has been linked with both antifibrotic and profibrotic outcomes in previous preclinical studies. “These different observations highlight the dual nature of IL-22 that likely is dictated by multiple factors including the tissue involved, pathologic environment, endogenous vs. exogenous IL-22 level, and the time of exposure.”
Prior research has left some questions unanswered, the investigators noted, because many studies have relied on exogenous administration of IL-22 in mouse models, some of which lack all the metabolic abnormalities observed in human disease. Furthermore, these mice were all male, which has prevented detection of possible sex-linked differences in IL-22–related pathophysiology, they added.
To address these gaps, the investigators conducted a series of experiments involving men and women with NAFLD, plus mice of both sexes with NAFLD induced by a high-fat diet, both wild-type and with knock-out of the IL-22 receptor.
Human data
To characterize IL-22 activity in men versus women with NAFLD, the investigators first analyzed two publicly available microarray datasets. These revealed notably increased expression of hepatic IL-22 mRNA in the livers of females compared with males. Supporting this finding, liver biopsies from 11 men and 9 women with NAFLD with similar levels of fibrosis showed significantly increased IL-22–producing cells in female patients compared with male patients.
“These results suggest a sexual dimorphic expression of IL-22 in the context of NAFLD,” the investigators wrote.
Mouse data
Echoing the human data, the livers of female wild-type mice with NAFLD had significantly greater IL-22 expression than male mice at both mRNA and protein levels.
Next, the investigators explored the effects of IL-22–receptor knockout. In addition to NAFLD, these knockout mice developed weight gain and metabolic alterations, especially insulin resistance, supporting previous work that highlighted the protective role of IL-22 against these outcomes. More relevant to the present study, female knockout mice had significantly worse hepatic liver injury, apoptosis, inflammation, and fibrosis than male knockout mice, suggesting that IL-22 signaling confers hepatoprotection in females but not males.
“These observations may suggest a regulation of IL-22 expression by the female sex hormone estrogen,” the investigators wrote. “Indeed, estrogen is known to modulate inflammatory responses in NAFLD, but the underlying mechanisms remain undefined. ... Further in vivo studies are warranted to investigate whether endogenous estrogen regulates hepatic IL-22 expression in the context of NAFLD.”
In the meantime, the present data may steer drug development.
“These findings should be considered in clinical trials testing IL-22–based therapeutic approaches in treatment of female vs. male subjects with NAFLD,” the investigators concluded.
The study was partially funded by the Canadian Liver Foundation and the Canadian Institutes of Health Research, the Bourse d’Exemption des Droits de Scolarité Supplémentaires from the Université de Montréal, the Canadian Network on Hepatitis, and others. The investigators disclosed no competing interests.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Dementia prevalence study reveals inequities
based on new U.S. data from The Health and Retirement Study (HRS).
These inequities likely stem from structural racism and income inequality, necessitating a multifaceted response at an institutional level, according to lead author Jennifer J. Manly, PhD, a professor of neuropsychology in neurology at the Gertrude H. Sergievsky Center and the Taub Institute for Research in Aging and Alzheimer’s Disease at Columbia University, New York.
A more representative dataset
Between 2001 and 2003, a subset of HRS participants underwent extensive neuropsychological assessment in the Aging, Demographics, and Memory Study (ADAMS), providing data which have since been cited by hundreds of published studies, the investigators wrote in JAMA Neurology. Those data, however, failed to accurately represent the U.S. population at the time, and have not been updated since.
“The ADAMS substudy was small, and the limited inclusion of Black, Hispanic, and American Indian or Alaska Native participants contributed to lack of precision of estimates among minoritized racial and ethnic groups that have been shown to experience a higher burden of cognitive impairment and dementia,” Dr. Manly and colleagues wrote.
The present analysis used a more representative dataset from HRS participants who were 65 years or older in 2016. From June 2016 to October 2017, 3,496 of these individuals underwent comprehensive neuropsychological test battery and informant interview, with dementia and MCI classified based on standard diagnostic criteria.
In total, 393 people were classified with dementia (10%), while 804 had MCI (22%), both of which approximate estimates reported by previous studies, according to the investigators. In further alignment with past research, age was a clear risk factor; each 5-year increment added 17% and 95% increased risk of MCI and dementia, respectively.
Compared with college-educated participants, individuals who did not graduate from high school had a 60% increased risk for both dementia (odds ratio, 1.6; 95% confidence interval, 1.1-2.3) and MCI (OR, 1.6; 95% CI, 1.2-2.2). Other educational strata were not associated with significant differences in risk.
Compared with White participants, Black individuals had an 80% increased risk of dementia (OR, 1.8; 95% CI, 1.2-2.7), but no increased risk of MCI. Conversely, non-White Hispanic individuals had a 40% increased risk of MCI (OR, 1.4; 95% CI, 1.0-2.0), but no increased risk of dementia, compared with White participants.
“Older adults racialized as Black and Hispanic are more likely to develop cognitive impairment and dementia because of historical and current structural racism and income inequality that restrict access to brain-health benefits and increase exposure to harm,” Dr. Manly said in a written comment.
These inequities deserve a comprehensive response, she added.
“Actions and policies that decrease discriminatory and aggressive policing policies, invest in schools that serve children that are racialized as Black and Hispanic, repair housing and economic inequalities, and provide equitable access to mental and physical health, can help to narrow disparities in later life cognitive impairment,” Dr. Manly said. “Two other areas of focus for policy makers are the shortage in the workforce of dementia care specialists, and paid family leave for caregiving.”
Acknowledging the needs of the historically underrepresented
Lealani Mae Acosta, MD, MPH, associate professor of neurology at Vanderbilt University Medical Center, Nashville, Tenn., applauded the investigators for their “conscious effort to expand representation of historically underrepresented minorities.”
The findings themselves support what has been previously reported, Dr. Acosta said in an interview, including the disproportionate burden of cognitive disorders among people of color and those with less education.
Clinicians need to recognize that certain patient groups face increased risks of cognitive disorders, and should be screened accordingly, Dr. Acosta said, noting that all aging patients should undergo such screening. The push for screening should also occur on a community level, along with efforts to build trust between at-risk populations and health care providers.
While Dr. Acosta reiterated the importance of these new data from Black and Hispanic individuals, she noted that gaps in representation remain, and methods of characterizing populations deserve refinement.
“I’m a little bit biased because I’m an Asian physician,” Dr. Acosta said. “As much as I’m glad that they’re highlighting these different disparities, there weren’t enough [participants in] specific subgroups like American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, to be able to identify specific trends within [those groups] that are, again, historically underrepresented patient populations.”
Grouping all people of Asian descent may also be an oversimplification, she added, as differences may exist between individuals originating from different countries.
“We always have to be careful about lumping certain groups together in analyses,” Dr. Acosta said. “That’s just another reminder to us – as clinicians, as researchers – that we need to do better by our patients by expanding research opportunities, and really studying these historically underrepresented populations.”
The study was supported by the National Institute on Aging. The investigators disclosed additional relationships with the Alzheimer’s Association and the National Institutes of Health. Dr. Acosta reported no relevant competing interests.
based on new U.S. data from The Health and Retirement Study (HRS).
These inequities likely stem from structural racism and income inequality, necessitating a multifaceted response at an institutional level, according to lead author Jennifer J. Manly, PhD, a professor of neuropsychology in neurology at the Gertrude H. Sergievsky Center and the Taub Institute for Research in Aging and Alzheimer’s Disease at Columbia University, New York.
A more representative dataset
Between 2001 and 2003, a subset of HRS participants underwent extensive neuropsychological assessment in the Aging, Demographics, and Memory Study (ADAMS), providing data which have since been cited by hundreds of published studies, the investigators wrote in JAMA Neurology. Those data, however, failed to accurately represent the U.S. population at the time, and have not been updated since.
“The ADAMS substudy was small, and the limited inclusion of Black, Hispanic, and American Indian or Alaska Native participants contributed to lack of precision of estimates among minoritized racial and ethnic groups that have been shown to experience a higher burden of cognitive impairment and dementia,” Dr. Manly and colleagues wrote.
The present analysis used a more representative dataset from HRS participants who were 65 years or older in 2016. From June 2016 to October 2017, 3,496 of these individuals underwent comprehensive neuropsychological test battery and informant interview, with dementia and MCI classified based on standard diagnostic criteria.
In total, 393 people were classified with dementia (10%), while 804 had MCI (22%), both of which approximate estimates reported by previous studies, according to the investigators. In further alignment with past research, age was a clear risk factor; each 5-year increment added 17% and 95% increased risk of MCI and dementia, respectively.
Compared with college-educated participants, individuals who did not graduate from high school had a 60% increased risk for both dementia (odds ratio, 1.6; 95% confidence interval, 1.1-2.3) and MCI (OR, 1.6; 95% CI, 1.2-2.2). Other educational strata were not associated with significant differences in risk.
Compared with White participants, Black individuals had an 80% increased risk of dementia (OR, 1.8; 95% CI, 1.2-2.7), but no increased risk of MCI. Conversely, non-White Hispanic individuals had a 40% increased risk of MCI (OR, 1.4; 95% CI, 1.0-2.0), but no increased risk of dementia, compared with White participants.
“Older adults racialized as Black and Hispanic are more likely to develop cognitive impairment and dementia because of historical and current structural racism and income inequality that restrict access to brain-health benefits and increase exposure to harm,” Dr. Manly said in a written comment.
These inequities deserve a comprehensive response, she added.
“Actions and policies that decrease discriminatory and aggressive policing policies, invest in schools that serve children that are racialized as Black and Hispanic, repair housing and economic inequalities, and provide equitable access to mental and physical health, can help to narrow disparities in later life cognitive impairment,” Dr. Manly said. “Two other areas of focus for policy makers are the shortage in the workforce of dementia care specialists, and paid family leave for caregiving.”
Acknowledging the needs of the historically underrepresented
Lealani Mae Acosta, MD, MPH, associate professor of neurology at Vanderbilt University Medical Center, Nashville, Tenn., applauded the investigators for their “conscious effort to expand representation of historically underrepresented minorities.”
The findings themselves support what has been previously reported, Dr. Acosta said in an interview, including the disproportionate burden of cognitive disorders among people of color and those with less education.
Clinicians need to recognize that certain patient groups face increased risks of cognitive disorders, and should be screened accordingly, Dr. Acosta said, noting that all aging patients should undergo such screening. The push for screening should also occur on a community level, along with efforts to build trust between at-risk populations and health care providers.
While Dr. Acosta reiterated the importance of these new data from Black and Hispanic individuals, she noted that gaps in representation remain, and methods of characterizing populations deserve refinement.
“I’m a little bit biased because I’m an Asian physician,” Dr. Acosta said. “As much as I’m glad that they’re highlighting these different disparities, there weren’t enough [participants in] specific subgroups like American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, to be able to identify specific trends within [those groups] that are, again, historically underrepresented patient populations.”
Grouping all people of Asian descent may also be an oversimplification, she added, as differences may exist between individuals originating from different countries.
“We always have to be careful about lumping certain groups together in analyses,” Dr. Acosta said. “That’s just another reminder to us – as clinicians, as researchers – that we need to do better by our patients by expanding research opportunities, and really studying these historically underrepresented populations.”
The study was supported by the National Institute on Aging. The investigators disclosed additional relationships with the Alzheimer’s Association and the National Institutes of Health. Dr. Acosta reported no relevant competing interests.
based on new U.S. data from The Health and Retirement Study (HRS).
These inequities likely stem from structural racism and income inequality, necessitating a multifaceted response at an institutional level, according to lead author Jennifer J. Manly, PhD, a professor of neuropsychology in neurology at the Gertrude H. Sergievsky Center and the Taub Institute for Research in Aging and Alzheimer’s Disease at Columbia University, New York.
A more representative dataset
Between 2001 and 2003, a subset of HRS participants underwent extensive neuropsychological assessment in the Aging, Demographics, and Memory Study (ADAMS), providing data which have since been cited by hundreds of published studies, the investigators wrote in JAMA Neurology. Those data, however, failed to accurately represent the U.S. population at the time, and have not been updated since.
“The ADAMS substudy was small, and the limited inclusion of Black, Hispanic, and American Indian or Alaska Native participants contributed to lack of precision of estimates among minoritized racial and ethnic groups that have been shown to experience a higher burden of cognitive impairment and dementia,” Dr. Manly and colleagues wrote.
The present analysis used a more representative dataset from HRS participants who were 65 years or older in 2016. From June 2016 to October 2017, 3,496 of these individuals underwent comprehensive neuropsychological test battery and informant interview, with dementia and MCI classified based on standard diagnostic criteria.
In total, 393 people were classified with dementia (10%), while 804 had MCI (22%), both of which approximate estimates reported by previous studies, according to the investigators. In further alignment with past research, age was a clear risk factor; each 5-year increment added 17% and 95% increased risk of MCI and dementia, respectively.
Compared with college-educated participants, individuals who did not graduate from high school had a 60% increased risk for both dementia (odds ratio, 1.6; 95% confidence interval, 1.1-2.3) and MCI (OR, 1.6; 95% CI, 1.2-2.2). Other educational strata were not associated with significant differences in risk.
Compared with White participants, Black individuals had an 80% increased risk of dementia (OR, 1.8; 95% CI, 1.2-2.7), but no increased risk of MCI. Conversely, non-White Hispanic individuals had a 40% increased risk of MCI (OR, 1.4; 95% CI, 1.0-2.0), but no increased risk of dementia, compared with White participants.
“Older adults racialized as Black and Hispanic are more likely to develop cognitive impairment and dementia because of historical and current structural racism and income inequality that restrict access to brain-health benefits and increase exposure to harm,” Dr. Manly said in a written comment.
These inequities deserve a comprehensive response, she added.
“Actions and policies that decrease discriminatory and aggressive policing policies, invest in schools that serve children that are racialized as Black and Hispanic, repair housing and economic inequalities, and provide equitable access to mental and physical health, can help to narrow disparities in later life cognitive impairment,” Dr. Manly said. “Two other areas of focus for policy makers are the shortage in the workforce of dementia care specialists, and paid family leave for caregiving.”
Acknowledging the needs of the historically underrepresented
Lealani Mae Acosta, MD, MPH, associate professor of neurology at Vanderbilt University Medical Center, Nashville, Tenn., applauded the investigators for their “conscious effort to expand representation of historically underrepresented minorities.”
The findings themselves support what has been previously reported, Dr. Acosta said in an interview, including the disproportionate burden of cognitive disorders among people of color and those with less education.
Clinicians need to recognize that certain patient groups face increased risks of cognitive disorders, and should be screened accordingly, Dr. Acosta said, noting that all aging patients should undergo such screening. The push for screening should also occur on a community level, along with efforts to build trust between at-risk populations and health care providers.
While Dr. Acosta reiterated the importance of these new data from Black and Hispanic individuals, she noted that gaps in representation remain, and methods of characterizing populations deserve refinement.
“I’m a little bit biased because I’m an Asian physician,” Dr. Acosta said. “As much as I’m glad that they’re highlighting these different disparities, there weren’t enough [participants in] specific subgroups like American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, to be able to identify specific trends within [those groups] that are, again, historically underrepresented patient populations.”
Grouping all people of Asian descent may also be an oversimplification, she added, as differences may exist between individuals originating from different countries.
“We always have to be careful about lumping certain groups together in analyses,” Dr. Acosta said. “That’s just another reminder to us – as clinicians, as researchers – that we need to do better by our patients by expanding research opportunities, and really studying these historically underrepresented populations.”
The study was supported by the National Institute on Aging. The investigators disclosed additional relationships with the Alzheimer’s Association and the National Institutes of Health. Dr. Acosta reported no relevant competing interests.
FROM JAMA NEUROLOGY
Novel YouTube study detects colonoscopy misinformation, guides better content creation
Don’t just sit there. Post something.
To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.
An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.
“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.
For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.
Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.
More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.
Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.
“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.
Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.
“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.
So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
How to create better content
While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.
“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”
More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.
First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.
“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.
The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.
The advent of social media ushered in the promise of a new age of information democratization. Unfortunately, the reality of increasingly accessible information – including misinformation – has disabused us of the notion that this increased accessibility is an unalloyed good. “Fake news” abounds, and in an era in which “truth” seems to be in the eye of the beholder – or influencer – medical misinformation appetizingly presented to the public is a particular hazard to public health. This is one of the first studies to offer an objective description of the medical information landscape as it pertains to the field of gastroenterology.
There is a tension between accessibility and quality of information within social media, the modern public forum. This study highlights that tension and serves both as a call-to-arms and a guide for experts on how to displace the amateurs and hucksters who are confusing those who’ve come to the forum not for entertainment but for information.
Jason M. Brown, MD, is assistant professor and Grady site fellowship director, division of digestive diseases, Emory University School of Medicine, Atlanta. Dr. Brown reported no relevant conflicts of interest.
The advent of social media ushered in the promise of a new age of information democratization. Unfortunately, the reality of increasingly accessible information – including misinformation – has disabused us of the notion that this increased accessibility is an unalloyed good. “Fake news” abounds, and in an era in which “truth” seems to be in the eye of the beholder – or influencer – medical misinformation appetizingly presented to the public is a particular hazard to public health. This is one of the first studies to offer an objective description of the medical information landscape as it pertains to the field of gastroenterology.
There is a tension between accessibility and quality of information within social media, the modern public forum. This study highlights that tension and serves both as a call-to-arms and a guide for experts on how to displace the amateurs and hucksters who are confusing those who’ve come to the forum not for entertainment but for information.
Jason M. Brown, MD, is assistant professor and Grady site fellowship director, division of digestive diseases, Emory University School of Medicine, Atlanta. Dr. Brown reported no relevant conflicts of interest.
The advent of social media ushered in the promise of a new age of information democratization. Unfortunately, the reality of increasingly accessible information – including misinformation – has disabused us of the notion that this increased accessibility is an unalloyed good. “Fake news” abounds, and in an era in which “truth” seems to be in the eye of the beholder – or influencer – medical misinformation appetizingly presented to the public is a particular hazard to public health. This is one of the first studies to offer an objective description of the medical information landscape as it pertains to the field of gastroenterology.
There is a tension between accessibility and quality of information within social media, the modern public forum. This study highlights that tension and serves both as a call-to-arms and a guide for experts on how to displace the amateurs and hucksters who are confusing those who’ve come to the forum not for entertainment but for information.
Jason M. Brown, MD, is assistant professor and Grady site fellowship director, division of digestive diseases, Emory University School of Medicine, Atlanta. Dr. Brown reported no relevant conflicts of interest.
Don’t just sit there. Post something.
To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.
An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.
“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.
For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.
Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.
More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.
Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.
“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.
Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.
“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.
So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
How to create better content
While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.
“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”
More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.
First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.
“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.
The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.
Don’t just sit there. Post something.
To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.
An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.
“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.
For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.
Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.
More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.
Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.
“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.
Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.
“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.
So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
How to create better content
While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.
“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”
More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.
First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.
“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.
The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.
FROM GASTRO HEP ADVANCES
Four commonly abused drugs linked with atrial fibrillation
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
FROM EUROPEAN HEART JOURNAL
More data suggest preexisting statin use improves COVID outcomes
Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.
They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.
“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”
He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.
In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.
To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.
The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.
Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).
A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.
“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”
Prospective studies needed before practice changes
How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.
“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”
Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.
Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”
Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.
“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.
The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.
Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.
They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.
“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”
He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.
In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.
To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.
The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.
Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).
A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.
“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”
Prospective studies needed before practice changes
How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.
“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”
Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.
Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”
Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.
“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.
The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.
Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.
They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.
“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”
He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.
In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.
To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.
The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.
Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).
A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.
“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”
Prospective studies needed before practice changes
How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.
“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”
Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.
Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”
Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.
“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.
The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.
FROM ANESTHESIOLOGY 2022
JAK inhibitors show no excess cardiovascular safety signal in French nationwide cohort
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
Apixaban outmatches rivaroxaban in patients with AFib and valvular heart disease
Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.
In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.
The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.
Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
Study results
Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).
Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.
The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.
“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
Head-to-head trial needed to change practice
Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”
Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.
“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”
Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.
The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.
Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.
“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.
On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.
More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.
This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.
Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.
In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.
The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.
Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
Study results
Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).
Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.
The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.
“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
Head-to-head trial needed to change practice
Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”
Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.
“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”
Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.
The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.
Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.
“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.
On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.
More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.
This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.
Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.
In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.
The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.
Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
Study results
Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).
Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.
The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.
“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
Head-to-head trial needed to change practice
Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”
Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.
“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”
Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.
The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.
Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.
“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.
On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.
More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.
This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE