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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.
How can clinicians distinguish food allergy and GERD in young kids?
The debate about a possible link between food allergy (FA) and pediatric gastroesophageal reflux disease (GERD) continues, and more, better-designed research is needed, a position paper by the European Academy of Allergy and Clinical Immunology reports.
The report offers consensus-based recommendations and a graphical decision pathway to guide providers through assessing and treating food allergy–related GERD. And the authors call for further, better-designed related research.
Food allergy and GERD are common in babies under 1 year of age and can lead to bothersome GERD, the authors write.
“An extensive literature search has found that whilst food proteins, in particular cow milk protein, can be a contributing factor to FA-associated” GERD, distinguishing between FA and non–FA-associated GERD is difficult, lead author Rosan Meyer, RD, PhD, senior lecturer at Imperial College London, and colleagues from the Academy task force on non-IgE mediated allergy, write in Pediatric Allergy and Immunology.
Consensus despite limited data
Dr. Meyer and colleagues developed clinical questions that addressed various aspects of the relationship between food allergy and GERD – pathophysiology, symptoms, diagnosis, dietary and medical management, prevalence, and impact on quality of life.
To address these issues, they systematically searched the literature for randomized controlled, observational, case-control, and retrospective studies of infants and children diagnosed with non-IgE gastrointestinal food allergies and GERD, published in English until February 2021.
Because of limited data in many of these areas, they used a modified Delphi method to reach consensus and provide practical advice on food allergy–associated GERD management.
The task force concludes:
- Food proteins, especially cow’s milk protein, can contribute to food allergy–associated GERD. The confirmation of food allergy is based on the elimination diet, always followed by reintroducing the offending allergen, and the diagnosis and treatment pathway should consider effects on quality of life.
- Breastfeeding should be supported in food allergy–associated GERD, and dietary advice should consider the potential nutritional impact on the breastfeeding mother. When breast milk is not available or is insufficient, formula and dietary advice to counteract the child’s nutrient deficiencies should be considered.
- Although some clarity exists about when GERD medications may be considered, they are often used inappropriately and may harm patients, especially infants.
Rigorous research needed
“Clinicians can use this algorithm to help them identify patients who may be affected by food allergy–related GERD,” Jonathan Tam, MD, medical director of the Gores Family Allergy Center at Children’s Hospital Los Angeles, told this news organization by email.
“Clinicians who suspect their patients may have food allergy–related GERD now have clearer guidance on how to systemically evaluate their patients,” added Dr. Tam, who was not involved in developing the report.
“Many allergists fear that patients may be labeled with a food allergy unnecessarily. Because no biomarkers or tests for food allergy–related GERD are available, elimination diets are a crucial part of the evaluation,” he said.
Dr. Tam added that the authors point out two key parts of a trial elimination: First, the trial should last at least 2 weeks, but full resolution may not occur until 6 weeks. Second, targeted elimination must be followed by reintroduction to confirm that the food was causing the symptoms, not that time itself may have been responsible for the clinical change.
“The authors’ note on allergy testing is important,” he said. “Allergy testing is not necessary when a clinician is concerned about food allergy–related GERD unless there are other associated atopic comorbidities, like eczema or IgE-mediated immediate food allergies.”
Jonathan M. Spergel, MD, PhD, chief of the allergy section at Children’s Hospital of Philadelphia, said in an email that families often ask whether food allergy is causing their child’s reflux.
“Both conditions are common and, in most cases, may not be related. As the report highlights, the risk of food allergy is increased if the patient has other atopic disease (atopic dermatitis), and standard allergy testing (skin testing, specific IgE) and IgG4 testing are not recommended,” he explained. “Food allergy in a patient with reflux can be considered if standard therapy is failing.”
Expert opinion on diagnosis and management
Dr. Spergel, also not involved in the report, joined the authors in advocating further, stronger studies. “While the expert opinion is a major strength,” he said, “with most available studies being neither randomized nor placebo-controlled, the true prevalence of food allergy reflux is unknown.”
Jay M. Portnoy, MD, specialist in pediatric allergy and immunology and medical director of telemedicine at Children’s Mercy Kansas City, said: “While most physicians believe that food allergy contributes to GERD, the evidence for the relationship is minimal. Reflux often occurs regardless of what food is eaten,” said Dr. Portnoy, who was not associated with the research.
Before removing a food from the diet, it’s important to determine whether that food is causing the problem, he urged.
“Blaming a food is easy. Food allergy is often suspected to cause symptoms it does not cause,” he said. “This unfounded blame can lead to unnecessary avoidance, reduce a family’s quality of life, and cause malnutrition.
“How a child is evaluated and treated depends as much on which physician they see as on whether the food is the culprit,” Dr. Portnoy said. “This report is an attempt to clarify the issues and to standardize an approach to the condition, so each provider evaluates and manages the condition in a consistent and evidence-based manner.
“It is important to see how well this report is incorporated into practice and whether following its guidance actually improves patient care,” Dr. Portnoy noted.
Funding information was not provided. Dr. Meyer and two coauthors report financial relationships with the nutritional health care industry. The full list can be found with the original article. The remaining authors and Dr. Tam, Dr. Spergel, and Dr. Portnoy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The debate about a possible link between food allergy (FA) and pediatric gastroesophageal reflux disease (GERD) continues, and more, better-designed research is needed, a position paper by the European Academy of Allergy and Clinical Immunology reports.
The report offers consensus-based recommendations and a graphical decision pathway to guide providers through assessing and treating food allergy–related GERD. And the authors call for further, better-designed related research.
Food allergy and GERD are common in babies under 1 year of age and can lead to bothersome GERD, the authors write.
“An extensive literature search has found that whilst food proteins, in particular cow milk protein, can be a contributing factor to FA-associated” GERD, distinguishing between FA and non–FA-associated GERD is difficult, lead author Rosan Meyer, RD, PhD, senior lecturer at Imperial College London, and colleagues from the Academy task force on non-IgE mediated allergy, write in Pediatric Allergy and Immunology.
Consensus despite limited data
Dr. Meyer and colleagues developed clinical questions that addressed various aspects of the relationship between food allergy and GERD – pathophysiology, symptoms, diagnosis, dietary and medical management, prevalence, and impact on quality of life.
To address these issues, they systematically searched the literature for randomized controlled, observational, case-control, and retrospective studies of infants and children diagnosed with non-IgE gastrointestinal food allergies and GERD, published in English until February 2021.
Because of limited data in many of these areas, they used a modified Delphi method to reach consensus and provide practical advice on food allergy–associated GERD management.
The task force concludes:
- Food proteins, especially cow’s milk protein, can contribute to food allergy–associated GERD. The confirmation of food allergy is based on the elimination diet, always followed by reintroducing the offending allergen, and the diagnosis and treatment pathway should consider effects on quality of life.
- Breastfeeding should be supported in food allergy–associated GERD, and dietary advice should consider the potential nutritional impact on the breastfeeding mother. When breast milk is not available or is insufficient, formula and dietary advice to counteract the child’s nutrient deficiencies should be considered.
- Although some clarity exists about when GERD medications may be considered, they are often used inappropriately and may harm patients, especially infants.
Rigorous research needed
“Clinicians can use this algorithm to help them identify patients who may be affected by food allergy–related GERD,” Jonathan Tam, MD, medical director of the Gores Family Allergy Center at Children’s Hospital Los Angeles, told this news organization by email.
“Clinicians who suspect their patients may have food allergy–related GERD now have clearer guidance on how to systemically evaluate their patients,” added Dr. Tam, who was not involved in developing the report.
“Many allergists fear that patients may be labeled with a food allergy unnecessarily. Because no biomarkers or tests for food allergy–related GERD are available, elimination diets are a crucial part of the evaluation,” he said.
Dr. Tam added that the authors point out two key parts of a trial elimination: First, the trial should last at least 2 weeks, but full resolution may not occur until 6 weeks. Second, targeted elimination must be followed by reintroduction to confirm that the food was causing the symptoms, not that time itself may have been responsible for the clinical change.
“The authors’ note on allergy testing is important,” he said. “Allergy testing is not necessary when a clinician is concerned about food allergy–related GERD unless there are other associated atopic comorbidities, like eczema or IgE-mediated immediate food allergies.”
Jonathan M. Spergel, MD, PhD, chief of the allergy section at Children’s Hospital of Philadelphia, said in an email that families often ask whether food allergy is causing their child’s reflux.
“Both conditions are common and, in most cases, may not be related. As the report highlights, the risk of food allergy is increased if the patient has other atopic disease (atopic dermatitis), and standard allergy testing (skin testing, specific IgE) and IgG4 testing are not recommended,” he explained. “Food allergy in a patient with reflux can be considered if standard therapy is failing.”
Expert opinion on diagnosis and management
Dr. Spergel, also not involved in the report, joined the authors in advocating further, stronger studies. “While the expert opinion is a major strength,” he said, “with most available studies being neither randomized nor placebo-controlled, the true prevalence of food allergy reflux is unknown.”
Jay M. Portnoy, MD, specialist in pediatric allergy and immunology and medical director of telemedicine at Children’s Mercy Kansas City, said: “While most physicians believe that food allergy contributes to GERD, the evidence for the relationship is minimal. Reflux often occurs regardless of what food is eaten,” said Dr. Portnoy, who was not associated with the research.
Before removing a food from the diet, it’s important to determine whether that food is causing the problem, he urged.
“Blaming a food is easy. Food allergy is often suspected to cause symptoms it does not cause,” he said. “This unfounded blame can lead to unnecessary avoidance, reduce a family’s quality of life, and cause malnutrition.
“How a child is evaluated and treated depends as much on which physician they see as on whether the food is the culprit,” Dr. Portnoy said. “This report is an attempt to clarify the issues and to standardize an approach to the condition, so each provider evaluates and manages the condition in a consistent and evidence-based manner.
“It is important to see how well this report is incorporated into practice and whether following its guidance actually improves patient care,” Dr. Portnoy noted.
Funding information was not provided. Dr. Meyer and two coauthors report financial relationships with the nutritional health care industry. The full list can be found with the original article. The remaining authors and Dr. Tam, Dr. Spergel, and Dr. Portnoy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The debate about a possible link between food allergy (FA) and pediatric gastroesophageal reflux disease (GERD) continues, and more, better-designed research is needed, a position paper by the European Academy of Allergy and Clinical Immunology reports.
The report offers consensus-based recommendations and a graphical decision pathway to guide providers through assessing and treating food allergy–related GERD. And the authors call for further, better-designed related research.
Food allergy and GERD are common in babies under 1 year of age and can lead to bothersome GERD, the authors write.
“An extensive literature search has found that whilst food proteins, in particular cow milk protein, can be a contributing factor to FA-associated” GERD, distinguishing between FA and non–FA-associated GERD is difficult, lead author Rosan Meyer, RD, PhD, senior lecturer at Imperial College London, and colleagues from the Academy task force on non-IgE mediated allergy, write in Pediatric Allergy and Immunology.
Consensus despite limited data
Dr. Meyer and colleagues developed clinical questions that addressed various aspects of the relationship between food allergy and GERD – pathophysiology, symptoms, diagnosis, dietary and medical management, prevalence, and impact on quality of life.
To address these issues, they systematically searched the literature for randomized controlled, observational, case-control, and retrospective studies of infants and children diagnosed with non-IgE gastrointestinal food allergies and GERD, published in English until February 2021.
Because of limited data in many of these areas, they used a modified Delphi method to reach consensus and provide practical advice on food allergy–associated GERD management.
The task force concludes:
- Food proteins, especially cow’s milk protein, can contribute to food allergy–associated GERD. The confirmation of food allergy is based on the elimination diet, always followed by reintroducing the offending allergen, and the diagnosis and treatment pathway should consider effects on quality of life.
- Breastfeeding should be supported in food allergy–associated GERD, and dietary advice should consider the potential nutritional impact on the breastfeeding mother. When breast milk is not available or is insufficient, formula and dietary advice to counteract the child’s nutrient deficiencies should be considered.
- Although some clarity exists about when GERD medications may be considered, they are often used inappropriately and may harm patients, especially infants.
Rigorous research needed
“Clinicians can use this algorithm to help them identify patients who may be affected by food allergy–related GERD,” Jonathan Tam, MD, medical director of the Gores Family Allergy Center at Children’s Hospital Los Angeles, told this news organization by email.
“Clinicians who suspect their patients may have food allergy–related GERD now have clearer guidance on how to systemically evaluate their patients,” added Dr. Tam, who was not involved in developing the report.
“Many allergists fear that patients may be labeled with a food allergy unnecessarily. Because no biomarkers or tests for food allergy–related GERD are available, elimination diets are a crucial part of the evaluation,” he said.
Dr. Tam added that the authors point out two key parts of a trial elimination: First, the trial should last at least 2 weeks, but full resolution may not occur until 6 weeks. Second, targeted elimination must be followed by reintroduction to confirm that the food was causing the symptoms, not that time itself may have been responsible for the clinical change.
“The authors’ note on allergy testing is important,” he said. “Allergy testing is not necessary when a clinician is concerned about food allergy–related GERD unless there are other associated atopic comorbidities, like eczema or IgE-mediated immediate food allergies.”
Jonathan M. Spergel, MD, PhD, chief of the allergy section at Children’s Hospital of Philadelphia, said in an email that families often ask whether food allergy is causing their child’s reflux.
“Both conditions are common and, in most cases, may not be related. As the report highlights, the risk of food allergy is increased if the patient has other atopic disease (atopic dermatitis), and standard allergy testing (skin testing, specific IgE) and IgG4 testing are not recommended,” he explained. “Food allergy in a patient with reflux can be considered if standard therapy is failing.”
Expert opinion on diagnosis and management
Dr. Spergel, also not involved in the report, joined the authors in advocating further, stronger studies. “While the expert opinion is a major strength,” he said, “with most available studies being neither randomized nor placebo-controlled, the true prevalence of food allergy reflux is unknown.”
Jay M. Portnoy, MD, specialist in pediatric allergy and immunology and medical director of telemedicine at Children’s Mercy Kansas City, said: “While most physicians believe that food allergy contributes to GERD, the evidence for the relationship is minimal. Reflux often occurs regardless of what food is eaten,” said Dr. Portnoy, who was not associated with the research.
Before removing a food from the diet, it’s important to determine whether that food is causing the problem, he urged.
“Blaming a food is easy. Food allergy is often suspected to cause symptoms it does not cause,” he said. “This unfounded blame can lead to unnecessary avoidance, reduce a family’s quality of life, and cause malnutrition.
“How a child is evaluated and treated depends as much on which physician they see as on whether the food is the culprit,” Dr. Portnoy said. “This report is an attempt to clarify the issues and to standardize an approach to the condition, so each provider evaluates and manages the condition in a consistent and evidence-based manner.
“It is important to see how well this report is incorporated into practice and whether following its guidance actually improves patient care,” Dr. Portnoy noted.
Funding information was not provided. Dr. Meyer and two coauthors report financial relationships with the nutritional health care industry. The full list can be found with the original article. The remaining authors and Dr. Tam, Dr. Spergel, and Dr. Portnoy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Flu, RSV infecting children at staggering rates
There has been no ebb in the flurry of respiratory illnesses infecting America’s youngest children. More pediatric wards across the country are announcing crises as beds reach capacity, the pediatric death toll jumped significantly in the past week, and sometimes children are being infected with more than one virus at a time.
In Oregon, for example, the governor announced an official state of emergency to help hospitals deal with the surge of respiratory viruses. Doernbecher Children’s Hospital in Portland, which houses half of all pediatric ICU beds statewide, moved to “crisis mode” and said every pediatric ICU bed was full, Oregon Public Broadcasting reported.
Last month, pediatricians nationwide called for a similar emergency declaration from the federal government to help them respond to the wave of illnesses, which include influenza and respiratory syncytial virus (RSV).
“What’s concerning to us are not only the number of infections, but the severity of these infections, leading to a high number of emergency room visits and hospitalizations,” pediatric infectious disease expert Oscar G. Gómez-Duarte, MD, PhD, said in a news release.
Five more pediatric deaths due to the flu were logged by the CDC in the past week, bringing the total for pediatric flu deaths this season to 12. Nearly 21 per 100,000 children ages 4 and under are being hospitalized for the flu, which is double the rate for children ages 5-17. Last year at this time, fewer than 1 child under age 4 per 100,000 were being hospitalized for the flu.
RSV rates are also stunningly high.
“If we look at CDC data, the RSV hospitalization rate is 10 times higher than usual for this point in the season,” American Medical Association Vice President Andrea Garcia, JD, said in this week’s AMA podcast. “And 171 out of every 100,000 infants younger than 6 months were hospitalized with RSV for the week ending Nov. 12. That is more than double the RSV hospitalization rate for newborns last year and seven times the rate in 2018, which is the last complete season we saw before the pandemic.”
Dr. Gómez-Duarte said hospitals are admitting children with respiratory illnesses who had otherwise been healthy, and sometimes they are even seeing patients with more than one illness.
“Yes, some children are getting what we call coinfections, where they become infected with more than one virus at a time. In some instances, a child becomes initially infected with flu, begins to recover, and subsequently comes down with rhinovirus (a common cold virus), RSV, or any other respiratory virus,” he said. “These coinfections tend to be more severe than when the child just has one infection.”
A version of this article first appeared on Medscape.com.
There has been no ebb in the flurry of respiratory illnesses infecting America’s youngest children. More pediatric wards across the country are announcing crises as beds reach capacity, the pediatric death toll jumped significantly in the past week, and sometimes children are being infected with more than one virus at a time.
In Oregon, for example, the governor announced an official state of emergency to help hospitals deal with the surge of respiratory viruses. Doernbecher Children’s Hospital in Portland, which houses half of all pediatric ICU beds statewide, moved to “crisis mode” and said every pediatric ICU bed was full, Oregon Public Broadcasting reported.
Last month, pediatricians nationwide called for a similar emergency declaration from the federal government to help them respond to the wave of illnesses, which include influenza and respiratory syncytial virus (RSV).
“What’s concerning to us are not only the number of infections, but the severity of these infections, leading to a high number of emergency room visits and hospitalizations,” pediatric infectious disease expert Oscar G. Gómez-Duarte, MD, PhD, said in a news release.
Five more pediatric deaths due to the flu were logged by the CDC in the past week, bringing the total for pediatric flu deaths this season to 12. Nearly 21 per 100,000 children ages 4 and under are being hospitalized for the flu, which is double the rate for children ages 5-17. Last year at this time, fewer than 1 child under age 4 per 100,000 were being hospitalized for the flu.
RSV rates are also stunningly high.
“If we look at CDC data, the RSV hospitalization rate is 10 times higher than usual for this point in the season,” American Medical Association Vice President Andrea Garcia, JD, said in this week’s AMA podcast. “And 171 out of every 100,000 infants younger than 6 months were hospitalized with RSV for the week ending Nov. 12. That is more than double the RSV hospitalization rate for newborns last year and seven times the rate in 2018, which is the last complete season we saw before the pandemic.”
Dr. Gómez-Duarte said hospitals are admitting children with respiratory illnesses who had otherwise been healthy, and sometimes they are even seeing patients with more than one illness.
“Yes, some children are getting what we call coinfections, where they become infected with more than one virus at a time. In some instances, a child becomes initially infected with flu, begins to recover, and subsequently comes down with rhinovirus (a common cold virus), RSV, or any other respiratory virus,” he said. “These coinfections tend to be more severe than when the child just has one infection.”
A version of this article first appeared on Medscape.com.
There has been no ebb in the flurry of respiratory illnesses infecting America’s youngest children. More pediatric wards across the country are announcing crises as beds reach capacity, the pediatric death toll jumped significantly in the past week, and sometimes children are being infected with more than one virus at a time.
In Oregon, for example, the governor announced an official state of emergency to help hospitals deal with the surge of respiratory viruses. Doernbecher Children’s Hospital in Portland, which houses half of all pediatric ICU beds statewide, moved to “crisis mode” and said every pediatric ICU bed was full, Oregon Public Broadcasting reported.
Last month, pediatricians nationwide called for a similar emergency declaration from the federal government to help them respond to the wave of illnesses, which include influenza and respiratory syncytial virus (RSV).
“What’s concerning to us are not only the number of infections, but the severity of these infections, leading to a high number of emergency room visits and hospitalizations,” pediatric infectious disease expert Oscar G. Gómez-Duarte, MD, PhD, said in a news release.
Five more pediatric deaths due to the flu were logged by the CDC in the past week, bringing the total for pediatric flu deaths this season to 12. Nearly 21 per 100,000 children ages 4 and under are being hospitalized for the flu, which is double the rate for children ages 5-17. Last year at this time, fewer than 1 child under age 4 per 100,000 were being hospitalized for the flu.
RSV rates are also stunningly high.
“If we look at CDC data, the RSV hospitalization rate is 10 times higher than usual for this point in the season,” American Medical Association Vice President Andrea Garcia, JD, said in this week’s AMA podcast. “And 171 out of every 100,000 infants younger than 6 months were hospitalized with RSV for the week ending Nov. 12. That is more than double the RSV hospitalization rate for newborns last year and seven times the rate in 2018, which is the last complete season we saw before the pandemic.”
Dr. Gómez-Duarte said hospitals are admitting children with respiratory illnesses who had otherwise been healthy, and sometimes they are even seeing patients with more than one illness.
“Yes, some children are getting what we call coinfections, where they become infected with more than one virus at a time. In some instances, a child becomes initially infected with flu, begins to recover, and subsequently comes down with rhinovirus (a common cold virus), RSV, or any other respiratory virus,” he said. “These coinfections tend to be more severe than when the child just has one infection.”
A version of this article first appeared on Medscape.com.
Covid vax prevents death in children regardless of variant
The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.
However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.
In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.
Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.
The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.
Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).
During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).
Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.
Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.
The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.
“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
Study limitations and strengths
The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.
Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.
The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
Data support value of vaccination, outside experts say
“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted.
The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.
However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.
Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.
“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”
“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”
Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.
The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.
The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.
However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.
In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.
Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.
The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.
Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).
During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).
Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.
Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.
The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.
“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
Study limitations and strengths
The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.
Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.
The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
Data support value of vaccination, outside experts say
“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted.
The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.
However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.
Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.
“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”
“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”
Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.
The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.
The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.
However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.
In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.
Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.
The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.
Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).
During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).
Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.
Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.
The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.
“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
Study limitations and strengths
The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.
Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.
The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
Data support value of vaccination, outside experts say
“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted.
The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.
However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.
Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.
“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”
“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”
Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.
The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.
FROM THE BMJ
With type 1 diabetes delay possible, focus now on screening
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
Migraine in children and teens: managing the pain
By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.
“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.
Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.
Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
Diagnosis
One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.
Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.
Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.
In addition, the headaches should exhibit at least two out of four features:
1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).
2. Be of moderate to severe intensity.
3. Have a pounding or throbbing quality.
4. Grow worse with activity or cause an avoidance of activity.
If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:
1. Are sensitive to light and sounds.
2. Are associated with nausea and/or vomiting.
A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.
“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.
Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.
“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
First line of treatment
Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.
“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”
The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.
Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.
Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.
However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.
Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B2) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.
“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.
For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.
A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.
For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.
Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
Lifestyle triggers
Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.
Migraine patients should also be mindful of their screen time, Dr. Kelley added.
“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.
As for other potential triggers of attacks, the evidence is mixed.
“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.
Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.
Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.
As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.
The difference for Mira has been extraordinary.
“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”
It’s only migraine
One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.
“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.
Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.
“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.
Some warning signs that further tests might be warranted, Dr. Kelley said, include:
- Headaches that wake a patient up in the middle of the night.
- Headaches that start first thing in the morning, especially those that include vomiting.
- A headache pattern that suddenly gets much worse.
- Certain symptoms that accompany the headache, such as tingling, numbness or double vision.
Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.
By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.
“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.
Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.
Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
Diagnosis
One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.
Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.
Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.
In addition, the headaches should exhibit at least two out of four features:
1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).
2. Be of moderate to severe intensity.
3. Have a pounding or throbbing quality.
4. Grow worse with activity or cause an avoidance of activity.
If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:
1. Are sensitive to light and sounds.
2. Are associated with nausea and/or vomiting.
A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.
“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.
Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.
“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
First line of treatment
Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.
“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”
The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.
Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.
Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.
However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.
Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B2) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.
“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.
For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.
A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.
For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.
Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
Lifestyle triggers
Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.
Migraine patients should also be mindful of their screen time, Dr. Kelley added.
“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.
As for other potential triggers of attacks, the evidence is mixed.
“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.
Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.
Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.
As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.
The difference for Mira has been extraordinary.
“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”
It’s only migraine
One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.
“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.
Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.
“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.
Some warning signs that further tests might be warranted, Dr. Kelley said, include:
- Headaches that wake a patient up in the middle of the night.
- Headaches that start first thing in the morning, especially those that include vomiting.
- A headache pattern that suddenly gets much worse.
- Certain symptoms that accompany the headache, such as tingling, numbness or double vision.
Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.
By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.
“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.
Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.
Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
Diagnosis
One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.
Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.
Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.
In addition, the headaches should exhibit at least two out of four features:
1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).
2. Be of moderate to severe intensity.
3. Have a pounding or throbbing quality.
4. Grow worse with activity or cause an avoidance of activity.
If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:
1. Are sensitive to light and sounds.
2. Are associated with nausea and/or vomiting.
A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.
“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.
Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.
“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
First line of treatment
Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.
“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”
The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.
Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.
Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.
However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.
Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B2) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.
“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.
For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.
A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.
For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.
Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
Lifestyle triggers
Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.
Migraine patients should also be mindful of their screen time, Dr. Kelley added.
“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.
As for other potential triggers of attacks, the evidence is mixed.
“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.
Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.
Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.
As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.
The difference for Mira has been extraordinary.
“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”
It’s only migraine
One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.
“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.
Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.
“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.
Some warning signs that further tests might be warranted, Dr. Kelley said, include:
- Headaches that wake a patient up in the middle of the night.
- Headaches that start first thing in the morning, especially those that include vomiting.
- A headache pattern that suddenly gets much worse.
- Certain symptoms that accompany the headache, such as tingling, numbness or double vision.
Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.
Obesity tied to worse brain health in children
CHICAGO – Higher weight and body mass index (BMI) in preadolescents are linked with poor brain health, new research suggests.
Poor brain health has been linked with obesity in adults, but little has been known about the link in children.
Lead author Simone Kaltenhauser, a postgraduate research fellow in radiology and biomedical imaging at the Yale School of Medicine, New Haven, Conn., presented her findings at the annual meeting of the Radiological Society of North America.
To represent the national sociodemographic makeup, the researchers used baseline information from the Adolescent Brain Cognitive Development (ABCD) study, which included 11,878 children aged 9 and 10 years from 21 centers across the United States.
This study included 5,169 children (51.9% girls). Children who had had traumatic brain injury, eating disorders, neurodevelopmental problems, and psychiatric diseases were excluded from the final analysis.
The researchers analyzed information from structural MRI and resting-state functional MRI, which allowed them to measure brain activity by detecting changes in blood flow.
“We analyzed the average fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD), and neurite density (ND) of 35 white matter (WM) tracts; cortical thickness and surface of 68 regions; and functional connectivity of 91 predefined network correlations,” the authors explained.
They adjusted for age, sex, race/ethnicity, handedness, and socioeconomic status. They used linear models to determine associations between weight and BMI z-scores and the imaging metrics.
Loss of white matter integrity
Among children with obesity, there was pervasive loss of white matter integrity and neurite density, cortical gray matter thinning, and decreased connectivity within and between networks that have been associated with impulse control and reward-based decision-making.
“These changes persisted in a similar pattern also 2 years later,” she said.
A member of the audience asked whether a reverse relationship might be at work – that poor brain health might drive obesity rather than the other way around.
Ms. Kaltenhauser agreed that other factors could be driving the link and acknowledged as a limitation that they did not have access to genetic information on the children.
Information on the effects of overweight and obesity is critical, especially in the United States, where an estimated 1 in 5 children are obese.
Ms. Kaltenhauser said she hopes her study raises awareness of potential brain health consequences as well as the physical consequences of childhood obesity.
Senior author Sam Payabvash, MD, a neuroradiologist and assistant professor of radiology and biomedical imaging at the Yale School of Medicine, said in a press release that the study may help explain the findings from previous studies that show an association between higher BMI in children and poor cognitive functioning and academic performance.
“The longitudinal ABCD study gives us the opportunity to observe any changes that occur in children with higher weight and BMI z-scores,” Dr. Payabvash said. “We’ll need to watch over the next 6-10 years.”
Avenues for future research
Amit B. Desai, MD, a neuroradiologist with Mayo Clinic in Jacksonville, Fla., who was not part of the study, said that while the research demonstrates an association between brain structure and BMI and obesity, “there may be other lurking variables.”
“What’s happening at an earlier stage in life could be causing both,” he said.
He noted that he would like to see future studies involving children at even earlier ages, along with investigations of the role of genetics or socioeconomic factors.
Including older children would be interesting as well, he said.
“Myelination doesn’t complete until you’re in your late teens or early 20s, so there are structural changes happening in the brain much later on into adolescence and early adulthood,” Dr. Desai said.
It would be premature, he said, to conclude from these findings that if children have obesity, there must be something wrong with their brain.
He would like to see whether there are changes in this link if a child is obese early on and later has normal weight or if a child has normal weight early and then becomes obese.
“It’s definitely an eye-opening study, but [it] needs additional work to expand upon it,” he said.
Ms. Kaltenhauser and Dr. Desai report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – Higher weight and body mass index (BMI) in preadolescents are linked with poor brain health, new research suggests.
Poor brain health has been linked with obesity in adults, but little has been known about the link in children.
Lead author Simone Kaltenhauser, a postgraduate research fellow in radiology and biomedical imaging at the Yale School of Medicine, New Haven, Conn., presented her findings at the annual meeting of the Radiological Society of North America.
To represent the national sociodemographic makeup, the researchers used baseline information from the Adolescent Brain Cognitive Development (ABCD) study, which included 11,878 children aged 9 and 10 years from 21 centers across the United States.
This study included 5,169 children (51.9% girls). Children who had had traumatic brain injury, eating disorders, neurodevelopmental problems, and psychiatric diseases were excluded from the final analysis.
The researchers analyzed information from structural MRI and resting-state functional MRI, which allowed them to measure brain activity by detecting changes in blood flow.
“We analyzed the average fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD), and neurite density (ND) of 35 white matter (WM) tracts; cortical thickness and surface of 68 regions; and functional connectivity of 91 predefined network correlations,” the authors explained.
They adjusted for age, sex, race/ethnicity, handedness, and socioeconomic status. They used linear models to determine associations between weight and BMI z-scores and the imaging metrics.
Loss of white matter integrity
Among children with obesity, there was pervasive loss of white matter integrity and neurite density, cortical gray matter thinning, and decreased connectivity within and between networks that have been associated with impulse control and reward-based decision-making.
“These changes persisted in a similar pattern also 2 years later,” she said.
A member of the audience asked whether a reverse relationship might be at work – that poor brain health might drive obesity rather than the other way around.
Ms. Kaltenhauser agreed that other factors could be driving the link and acknowledged as a limitation that they did not have access to genetic information on the children.
Information on the effects of overweight and obesity is critical, especially in the United States, where an estimated 1 in 5 children are obese.
Ms. Kaltenhauser said she hopes her study raises awareness of potential brain health consequences as well as the physical consequences of childhood obesity.
Senior author Sam Payabvash, MD, a neuroradiologist and assistant professor of radiology and biomedical imaging at the Yale School of Medicine, said in a press release that the study may help explain the findings from previous studies that show an association between higher BMI in children and poor cognitive functioning and academic performance.
“The longitudinal ABCD study gives us the opportunity to observe any changes that occur in children with higher weight and BMI z-scores,” Dr. Payabvash said. “We’ll need to watch over the next 6-10 years.”
Avenues for future research
Amit B. Desai, MD, a neuroradiologist with Mayo Clinic in Jacksonville, Fla., who was not part of the study, said that while the research demonstrates an association between brain structure and BMI and obesity, “there may be other lurking variables.”
“What’s happening at an earlier stage in life could be causing both,” he said.
He noted that he would like to see future studies involving children at even earlier ages, along with investigations of the role of genetics or socioeconomic factors.
Including older children would be interesting as well, he said.
“Myelination doesn’t complete until you’re in your late teens or early 20s, so there are structural changes happening in the brain much later on into adolescence and early adulthood,” Dr. Desai said.
It would be premature, he said, to conclude from these findings that if children have obesity, there must be something wrong with their brain.
He would like to see whether there are changes in this link if a child is obese early on and later has normal weight or if a child has normal weight early and then becomes obese.
“It’s definitely an eye-opening study, but [it] needs additional work to expand upon it,” he said.
Ms. Kaltenhauser and Dr. Desai report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – Higher weight and body mass index (BMI) in preadolescents are linked with poor brain health, new research suggests.
Poor brain health has been linked with obesity in adults, but little has been known about the link in children.
Lead author Simone Kaltenhauser, a postgraduate research fellow in radiology and biomedical imaging at the Yale School of Medicine, New Haven, Conn., presented her findings at the annual meeting of the Radiological Society of North America.
To represent the national sociodemographic makeup, the researchers used baseline information from the Adolescent Brain Cognitive Development (ABCD) study, which included 11,878 children aged 9 and 10 years from 21 centers across the United States.
This study included 5,169 children (51.9% girls). Children who had had traumatic brain injury, eating disorders, neurodevelopmental problems, and psychiatric diseases were excluded from the final analysis.
The researchers analyzed information from structural MRI and resting-state functional MRI, which allowed them to measure brain activity by detecting changes in blood flow.
“We analyzed the average fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD), and neurite density (ND) of 35 white matter (WM) tracts; cortical thickness and surface of 68 regions; and functional connectivity of 91 predefined network correlations,” the authors explained.
They adjusted for age, sex, race/ethnicity, handedness, and socioeconomic status. They used linear models to determine associations between weight and BMI z-scores and the imaging metrics.
Loss of white matter integrity
Among children with obesity, there was pervasive loss of white matter integrity and neurite density, cortical gray matter thinning, and decreased connectivity within and between networks that have been associated with impulse control and reward-based decision-making.
“These changes persisted in a similar pattern also 2 years later,” she said.
A member of the audience asked whether a reverse relationship might be at work – that poor brain health might drive obesity rather than the other way around.
Ms. Kaltenhauser agreed that other factors could be driving the link and acknowledged as a limitation that they did not have access to genetic information on the children.
Information on the effects of overweight and obesity is critical, especially in the United States, where an estimated 1 in 5 children are obese.
Ms. Kaltenhauser said she hopes her study raises awareness of potential brain health consequences as well as the physical consequences of childhood obesity.
Senior author Sam Payabvash, MD, a neuroradiologist and assistant professor of radiology and biomedical imaging at the Yale School of Medicine, said in a press release that the study may help explain the findings from previous studies that show an association between higher BMI in children and poor cognitive functioning and academic performance.
“The longitudinal ABCD study gives us the opportunity to observe any changes that occur in children with higher weight and BMI z-scores,” Dr. Payabvash said. “We’ll need to watch over the next 6-10 years.”
Avenues for future research
Amit B. Desai, MD, a neuroradiologist with Mayo Clinic in Jacksonville, Fla., who was not part of the study, said that while the research demonstrates an association between brain structure and BMI and obesity, “there may be other lurking variables.”
“What’s happening at an earlier stage in life could be causing both,” he said.
He noted that he would like to see future studies involving children at even earlier ages, along with investigations of the role of genetics or socioeconomic factors.
Including older children would be interesting as well, he said.
“Myelination doesn’t complete until you’re in your late teens or early 20s, so there are structural changes happening in the brain much later on into adolescence and early adulthood,” Dr. Desai said.
It would be premature, he said, to conclude from these findings that if children have obesity, there must be something wrong with their brain.
He would like to see whether there are changes in this link if a child is obese early on and later has normal weight or if a child has normal weight early and then becomes obese.
“It’s definitely an eye-opening study, but [it] needs additional work to expand upon it,” he said.
Ms. Kaltenhauser and Dr. Desai report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT RSNA 2022
The surprising failure of vitamin D in deficient kids
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
My basic gripe is that you’ve got all these observational studies linking lower levels of vitamin D to everything from dementia to falls to cancer to COVID infection, and then you do a big randomized trial of supplementation and don’t see an effect.
And the explanation is that vitamin D is not necessarily the thing causing these bad outcomes; it’s a bystander – a canary in the coal mine. Your vitamin D level is a marker of your lifestyle; it’s higher in people who eat healthier foods, who exercise, and who spend more time out in the sun.
And yet ... if you were to ask me whether supplementing vitamin D in children with vitamin D deficiency would help them grow better and be healthier, I probably would have been on board for the idea.
And, it looks like, I would have been wrong.
Yes, it’s another negative randomized trial of vitamin D supplementation to add to the seemingly ever-growing body of literature suggesting that your money is better spent on a day at the park rather than buying D3 from your local GNC.
We are talking about this study, appearing in JAMA Pediatrics.
Briefly, 8,851 children from around Ulaanbaatar, Mongolia, were randomized to receive 14,000 international units of vitamin D3 or placebo every week for 3 years.
Before we get into the results of the study, I need to point out that this part of Mongolia has a high rate of vitamin D deficiency. Beyond that, a prior observational study by these authors had shown that lower vitamin D levels were linked to the risk of acquiring latent tuberculosis infection in this area. Other studies have linked vitamin D deficiency with poorer growth metrics in children. Given the global scourge that is TB (around 2 million deaths a year) and childhood malnutrition (around 10% of children around the world), vitamin D supplementation is incredibly attractive as a public health intervention. It is relatively low on side effects and, importantly, it is cheap – and thus scalable.
Back to the study. These kids had pretty poor vitamin D levels at baseline; 95% of them were deficient, based on the accepted standard of levels less than 20 ng/mL. Over 30% were severely deficient, with levels less than 10 ng/mL.
The initial purpose of this study was to see if supplementation would prevent TB, but that analysis, which was published a few months ago, was negative. Vitamin D levels went up dramatically in the intervention group – they were taking their pills – but there was no difference in the rate of latent TB infection, active TB, other respiratory infections, or even serum interferon gamma levels.
Nothing.
But to be fair, the TB seroconversion rate was lower than expected, potentially leading to an underpowered study.
Which brings us to the just-published analysis which moves away from infectious disease to something where vitamin D should have some stronger footing: growth.
Would the kids who were randomized to vitamin D, those same kids who got their vitamin D levels into the normal range over 3 years of supplementation, grow more or grow better than the kids who didn’t?
And, unfortunately, the answer is still no.
At the end of follow-up, height z scores were not different between the groups. BMI z scores were not different between the groups. Pubertal development was not different between the groups. This was true not only overall, but across various subgroups, including analyses of those kids who had vitamin D levels less than 10 ng/mL to start with.
So, what’s going on? There are two very broad possibilities we can endorse. First, there’s the idea that vitamin D supplementation simply doesn’t do much for health. This is supported, now, by a long string of large clinical trials that show no effect across a variety of disease states and predisease states. In other words, the observational data linking low vitamin D to bad outcomes is correlation, not causation.
Or we can take the tack of some vitamin D apologists and decide that this trial just got it wrong. Perhaps the dose wasn’t given correctly, or 3 years isn’t long enough to see a real difference, or the growth metrics were wrong, or vitamin D needs to be given alongside something else to really work and so on. This is fine; no study is perfect and there is always something to criticize, believe me. But we need to be careful not to fall into the baby-and-bathwater fallacy. Just because we think a study could have done something better, or differently, doesn’t mean we can ignore all the results. And as each new randomized trial of vitamin D supplementation comes out, it’s getting harder and harder to believe that these trialists keep getting their methods wrong. Maybe they are just testing something that doesn’t work.
What to do? Well, it should be obvious. If low vitamin D levels are linked to TB rates and poor growth but supplementation doesn’t fix the problem, then we have to fix what is upstream of the problem. We need to boost vitamin D levels not through supplements, but through nutrition, exercise, activity, and getting outside. That’s a randomized trial you can sign me up for any day.
Dr. Wilson is associate professor, department of medicine, Yale University, New Haven, Conn. He reported no relevant conflicts of interest.
A version of this video transcript first appeared on Medscape.com.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
My basic gripe is that you’ve got all these observational studies linking lower levels of vitamin D to everything from dementia to falls to cancer to COVID infection, and then you do a big randomized trial of supplementation and don’t see an effect.
And the explanation is that vitamin D is not necessarily the thing causing these bad outcomes; it’s a bystander – a canary in the coal mine. Your vitamin D level is a marker of your lifestyle; it’s higher in people who eat healthier foods, who exercise, and who spend more time out in the sun.
And yet ... if you were to ask me whether supplementing vitamin D in children with vitamin D deficiency would help them grow better and be healthier, I probably would have been on board for the idea.
And, it looks like, I would have been wrong.
Yes, it’s another negative randomized trial of vitamin D supplementation to add to the seemingly ever-growing body of literature suggesting that your money is better spent on a day at the park rather than buying D3 from your local GNC.
We are talking about this study, appearing in JAMA Pediatrics.
Briefly, 8,851 children from around Ulaanbaatar, Mongolia, were randomized to receive 14,000 international units of vitamin D3 or placebo every week for 3 years.
Before we get into the results of the study, I need to point out that this part of Mongolia has a high rate of vitamin D deficiency. Beyond that, a prior observational study by these authors had shown that lower vitamin D levels were linked to the risk of acquiring latent tuberculosis infection in this area. Other studies have linked vitamin D deficiency with poorer growth metrics in children. Given the global scourge that is TB (around 2 million deaths a year) and childhood malnutrition (around 10% of children around the world), vitamin D supplementation is incredibly attractive as a public health intervention. It is relatively low on side effects and, importantly, it is cheap – and thus scalable.
Back to the study. These kids had pretty poor vitamin D levels at baseline; 95% of them were deficient, based on the accepted standard of levels less than 20 ng/mL. Over 30% were severely deficient, with levels less than 10 ng/mL.
The initial purpose of this study was to see if supplementation would prevent TB, but that analysis, which was published a few months ago, was negative. Vitamin D levels went up dramatically in the intervention group – they were taking their pills – but there was no difference in the rate of latent TB infection, active TB, other respiratory infections, or even serum interferon gamma levels.
Nothing.
But to be fair, the TB seroconversion rate was lower than expected, potentially leading to an underpowered study.
Which brings us to the just-published analysis which moves away from infectious disease to something where vitamin D should have some stronger footing: growth.
Would the kids who were randomized to vitamin D, those same kids who got their vitamin D levels into the normal range over 3 years of supplementation, grow more or grow better than the kids who didn’t?
And, unfortunately, the answer is still no.
At the end of follow-up, height z scores were not different between the groups. BMI z scores were not different between the groups. Pubertal development was not different between the groups. This was true not only overall, but across various subgroups, including analyses of those kids who had vitamin D levels less than 10 ng/mL to start with.
So, what’s going on? There are two very broad possibilities we can endorse. First, there’s the idea that vitamin D supplementation simply doesn’t do much for health. This is supported, now, by a long string of large clinical trials that show no effect across a variety of disease states and predisease states. In other words, the observational data linking low vitamin D to bad outcomes is correlation, not causation.
Or we can take the tack of some vitamin D apologists and decide that this trial just got it wrong. Perhaps the dose wasn’t given correctly, or 3 years isn’t long enough to see a real difference, or the growth metrics were wrong, or vitamin D needs to be given alongside something else to really work and so on. This is fine; no study is perfect and there is always something to criticize, believe me. But we need to be careful not to fall into the baby-and-bathwater fallacy. Just because we think a study could have done something better, or differently, doesn’t mean we can ignore all the results. And as each new randomized trial of vitamin D supplementation comes out, it’s getting harder and harder to believe that these trialists keep getting their methods wrong. Maybe they are just testing something that doesn’t work.
What to do? Well, it should be obvious. If low vitamin D levels are linked to TB rates and poor growth but supplementation doesn’t fix the problem, then we have to fix what is upstream of the problem. We need to boost vitamin D levels not through supplements, but through nutrition, exercise, activity, and getting outside. That’s a randomized trial you can sign me up for any day.
Dr. Wilson is associate professor, department of medicine, Yale University, New Haven, Conn. He reported no relevant conflicts of interest.
A version of this video transcript first appeared on Medscape.com.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
My basic gripe is that you’ve got all these observational studies linking lower levels of vitamin D to everything from dementia to falls to cancer to COVID infection, and then you do a big randomized trial of supplementation and don’t see an effect.
And the explanation is that vitamin D is not necessarily the thing causing these bad outcomes; it’s a bystander – a canary in the coal mine. Your vitamin D level is a marker of your lifestyle; it’s higher in people who eat healthier foods, who exercise, and who spend more time out in the sun.
And yet ... if you were to ask me whether supplementing vitamin D in children with vitamin D deficiency would help them grow better and be healthier, I probably would have been on board for the idea.
And, it looks like, I would have been wrong.
Yes, it’s another negative randomized trial of vitamin D supplementation to add to the seemingly ever-growing body of literature suggesting that your money is better spent on a day at the park rather than buying D3 from your local GNC.
We are talking about this study, appearing in JAMA Pediatrics.
Briefly, 8,851 children from around Ulaanbaatar, Mongolia, were randomized to receive 14,000 international units of vitamin D3 or placebo every week for 3 years.
Before we get into the results of the study, I need to point out that this part of Mongolia has a high rate of vitamin D deficiency. Beyond that, a prior observational study by these authors had shown that lower vitamin D levels were linked to the risk of acquiring latent tuberculosis infection in this area. Other studies have linked vitamin D deficiency with poorer growth metrics in children. Given the global scourge that is TB (around 2 million deaths a year) and childhood malnutrition (around 10% of children around the world), vitamin D supplementation is incredibly attractive as a public health intervention. It is relatively low on side effects and, importantly, it is cheap – and thus scalable.
Back to the study. These kids had pretty poor vitamin D levels at baseline; 95% of them were deficient, based on the accepted standard of levels less than 20 ng/mL. Over 30% were severely deficient, with levels less than 10 ng/mL.
The initial purpose of this study was to see if supplementation would prevent TB, but that analysis, which was published a few months ago, was negative. Vitamin D levels went up dramatically in the intervention group – they were taking their pills – but there was no difference in the rate of latent TB infection, active TB, other respiratory infections, or even serum interferon gamma levels.
Nothing.
But to be fair, the TB seroconversion rate was lower than expected, potentially leading to an underpowered study.
Which brings us to the just-published analysis which moves away from infectious disease to something where vitamin D should have some stronger footing: growth.
Would the kids who were randomized to vitamin D, those same kids who got their vitamin D levels into the normal range over 3 years of supplementation, grow more or grow better than the kids who didn’t?
And, unfortunately, the answer is still no.
At the end of follow-up, height z scores were not different between the groups. BMI z scores were not different between the groups. Pubertal development was not different between the groups. This was true not only overall, but across various subgroups, including analyses of those kids who had vitamin D levels less than 10 ng/mL to start with.
So, what’s going on? There are two very broad possibilities we can endorse. First, there’s the idea that vitamin D supplementation simply doesn’t do much for health. This is supported, now, by a long string of large clinical trials that show no effect across a variety of disease states and predisease states. In other words, the observational data linking low vitamin D to bad outcomes is correlation, not causation.
Or we can take the tack of some vitamin D apologists and decide that this trial just got it wrong. Perhaps the dose wasn’t given correctly, or 3 years isn’t long enough to see a real difference, or the growth metrics were wrong, or vitamin D needs to be given alongside something else to really work and so on. This is fine; no study is perfect and there is always something to criticize, believe me. But we need to be careful not to fall into the baby-and-bathwater fallacy. Just because we think a study could have done something better, or differently, doesn’t mean we can ignore all the results. And as each new randomized trial of vitamin D supplementation comes out, it’s getting harder and harder to believe that these trialists keep getting their methods wrong. Maybe they are just testing something that doesn’t work.
What to do? Well, it should be obvious. If low vitamin D levels are linked to TB rates and poor growth but supplementation doesn’t fix the problem, then we have to fix what is upstream of the problem. We need to boost vitamin D levels not through supplements, but through nutrition, exercise, activity, and getting outside. That’s a randomized trial you can sign me up for any day.
Dr. Wilson is associate professor, department of medicine, Yale University, New Haven, Conn. He reported no relevant conflicts of interest.
A version of this video transcript first appeared on Medscape.com.
U.S. flu activity already at mid-season levels
according to the Centers of Disease Control and Prevention.
Nationally, 6% of all outpatient visits were because of flu or flu-like illness for the week of Nov. 13-19, up from 5.8% the previous week, the CDC’s Influenza Division said in its weekly FluView report.
Those figures are the highest recorded in November since 2009, but the peak of the 2009-10 flu season occurred even earlier – the week of Oct. 18-24 – and the rate of flu-like illness had already dropped to just over 4.0% by Nov. 15-21 that year and continued to drop thereafter.
Although COVID-19 and respiratory syncytial virus (RSV) are included in the data from the CDC’s Outpatient Influenza-like Illness Surveillance Network, the agency did note that “seasonal influenza activity is elevated across the country” and estimated that “there have been at least 6.2 million illnesses, 53,000 hospitalizations, and 2,900 deaths from flu” during the 2022-23 season.
Total flu deaths include 11 reported in children as of Nov. 19, and children ages 0-4 had a higher proportion of visits for flu like-illness than other age groups.
The agency also said the cumulative hospitalization rate of 11.3 per 100,000 population “is higher than the rate observed in [the corresponding week of] every previous season since 2010-2011.” Adults 65 years and older have the highest cumulative rate, 25.9 per 100,000, for this year, compared with 20.7 for children 0-4; 11.1 for adults 50-64; 10.3 for children 5-17; and 5.6 for adults 18-49 years old, the CDC said.
A version of this article first appeared on WebMD.com.
according to the Centers of Disease Control and Prevention.
Nationally, 6% of all outpatient visits were because of flu or flu-like illness for the week of Nov. 13-19, up from 5.8% the previous week, the CDC’s Influenza Division said in its weekly FluView report.
Those figures are the highest recorded in November since 2009, but the peak of the 2009-10 flu season occurred even earlier – the week of Oct. 18-24 – and the rate of flu-like illness had already dropped to just over 4.0% by Nov. 15-21 that year and continued to drop thereafter.
Although COVID-19 and respiratory syncytial virus (RSV) are included in the data from the CDC’s Outpatient Influenza-like Illness Surveillance Network, the agency did note that “seasonal influenza activity is elevated across the country” and estimated that “there have been at least 6.2 million illnesses, 53,000 hospitalizations, and 2,900 deaths from flu” during the 2022-23 season.
Total flu deaths include 11 reported in children as of Nov. 19, and children ages 0-4 had a higher proportion of visits for flu like-illness than other age groups.
The agency also said the cumulative hospitalization rate of 11.3 per 100,000 population “is higher than the rate observed in [the corresponding week of] every previous season since 2010-2011.” Adults 65 years and older have the highest cumulative rate, 25.9 per 100,000, for this year, compared with 20.7 for children 0-4; 11.1 for adults 50-64; 10.3 for children 5-17; and 5.6 for adults 18-49 years old, the CDC said.
A version of this article first appeared on WebMD.com.
according to the Centers of Disease Control and Prevention.
Nationally, 6% of all outpatient visits were because of flu or flu-like illness for the week of Nov. 13-19, up from 5.8% the previous week, the CDC’s Influenza Division said in its weekly FluView report.
Those figures are the highest recorded in November since 2009, but the peak of the 2009-10 flu season occurred even earlier – the week of Oct. 18-24 – and the rate of flu-like illness had already dropped to just over 4.0% by Nov. 15-21 that year and continued to drop thereafter.
Although COVID-19 and respiratory syncytial virus (RSV) are included in the data from the CDC’s Outpatient Influenza-like Illness Surveillance Network, the agency did note that “seasonal influenza activity is elevated across the country” and estimated that “there have been at least 6.2 million illnesses, 53,000 hospitalizations, and 2,900 deaths from flu” during the 2022-23 season.
Total flu deaths include 11 reported in children as of Nov. 19, and children ages 0-4 had a higher proportion of visits for flu like-illness than other age groups.
The agency also said the cumulative hospitalization rate of 11.3 per 100,000 population “is higher than the rate observed in [the corresponding week of] every previous season since 2010-2011.” Adults 65 years and older have the highest cumulative rate, 25.9 per 100,000, for this year, compared with 20.7 for children 0-4; 11.1 for adults 50-64; 10.3 for children 5-17; and 5.6 for adults 18-49 years old, the CDC said.
A version of this article first appeared on WebMD.com.
Your patients are rotting their teeth with vaping
Primary care physicians, and especially pediatricians, should consider telling their patients about the long-term oral health problems associated with vaping.
A new study found that patients who use vapes were at a higher risk of developing tooth decay and periodontal disease.
Vapes were introduced to the U.S. market in 2006 as an alternative to conventional cigarettes and have become widely popular among youth. According to a 2022 survey from the U.S. Centers for Disease Control and Prevention, 2.55 million middle and high school students in this country reported using the devices in the previous 30 days.
The new study, published in the Journal of the American Dental Association, expands on an initial case series published in 2020 of patients who reported use of vapes and who had severe dental decay. Karina Irusa, BDS, assistant professor of comprehensive care at Tufts University, Boston, and lead author of the case series, wanted to investigate whether her initial findings would apply to a large population of vape users.
For the new study, Dr. Irusa and colleagues collected data on 13,216 patients aged 16-40 who attended Tufts dental clinics between 2019 and 2021. All patients had received a diagnosis of tooth decay, had a tooth decay risk assessment on record, and had answered “yes” or “no” to use of vapes in a health history questionnaire.
Patients had records on file of varying types of dental lesions, cavities filled within the previous 3 years, heavy plaque on teeth, inadequate brushing and flushing, and a self-report of recreational drug use and frequent snacking. If patients had these factors on their file, they were at high risk of developing decay that leads to cavities.
The study found that 79% of patients who responded “yes” to being a current user of vapes were at high risk for dental decay, compared with 60% of those who did not report using the devices.
Materials in the vaping liquids further cause an inflammatory response that disrupts an individual’s internal microbiome, according to numerous studies.
“All the ingredients of vaping are surely a recipe for overgrowth of cavities causing bacteria,” said Jennifer Genuardi, MD, an internist and pediatrician at federally qualified community health center Urban Health Plan, in New York, who was not involved in the study.
Dr. Irusa said information on patient’s vaping habits should be included in routine dental and medical history questionnaires as part of their overall electronic health record.
“Decay in its severe form not only affects one’s ability to eat but affects facial aesthetics and self-esteem as well,” Dr. Irusa said.
Dr. Genuardi called the findings unsurprising.
“We are learning daily more and more about the dangers of vaping,” Dr. Genuardi said. “There’s a focus of today’s research on the effect of actions on our microbiome and the subsequent effects on our health.”
Dr. Genuardi also said many of her teenage patients do not enjoy dental visits or having cavities filled, which could serve as a useful deterrent to vaping for a demographic that has been targeted with marketing from vape manufacturers.
“Cavity formation and the experience of having cavities filled is an experience teens can identify with, so this to me seems like perhaps an even more effective angle to try to curb this unhealthy behavior of vaping,” Dr. Genuardi said.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Primary care physicians, and especially pediatricians, should consider telling their patients about the long-term oral health problems associated with vaping.
A new study found that patients who use vapes were at a higher risk of developing tooth decay and periodontal disease.
Vapes were introduced to the U.S. market in 2006 as an alternative to conventional cigarettes and have become widely popular among youth. According to a 2022 survey from the U.S. Centers for Disease Control and Prevention, 2.55 million middle and high school students in this country reported using the devices in the previous 30 days.
The new study, published in the Journal of the American Dental Association, expands on an initial case series published in 2020 of patients who reported use of vapes and who had severe dental decay. Karina Irusa, BDS, assistant professor of comprehensive care at Tufts University, Boston, and lead author of the case series, wanted to investigate whether her initial findings would apply to a large population of vape users.
For the new study, Dr. Irusa and colleagues collected data on 13,216 patients aged 16-40 who attended Tufts dental clinics between 2019 and 2021. All patients had received a diagnosis of tooth decay, had a tooth decay risk assessment on record, and had answered “yes” or “no” to use of vapes in a health history questionnaire.
Patients had records on file of varying types of dental lesions, cavities filled within the previous 3 years, heavy plaque on teeth, inadequate brushing and flushing, and a self-report of recreational drug use and frequent snacking. If patients had these factors on their file, they were at high risk of developing decay that leads to cavities.
The study found that 79% of patients who responded “yes” to being a current user of vapes were at high risk for dental decay, compared with 60% of those who did not report using the devices.
Materials in the vaping liquids further cause an inflammatory response that disrupts an individual’s internal microbiome, according to numerous studies.
“All the ingredients of vaping are surely a recipe for overgrowth of cavities causing bacteria,” said Jennifer Genuardi, MD, an internist and pediatrician at federally qualified community health center Urban Health Plan, in New York, who was not involved in the study.
Dr. Irusa said information on patient’s vaping habits should be included in routine dental and medical history questionnaires as part of their overall electronic health record.
“Decay in its severe form not only affects one’s ability to eat but affects facial aesthetics and self-esteem as well,” Dr. Irusa said.
Dr. Genuardi called the findings unsurprising.
“We are learning daily more and more about the dangers of vaping,” Dr. Genuardi said. “There’s a focus of today’s research on the effect of actions on our microbiome and the subsequent effects on our health.”
Dr. Genuardi also said many of her teenage patients do not enjoy dental visits or having cavities filled, which could serve as a useful deterrent to vaping for a demographic that has been targeted with marketing from vape manufacturers.
“Cavity formation and the experience of having cavities filled is an experience teens can identify with, so this to me seems like perhaps an even more effective angle to try to curb this unhealthy behavior of vaping,” Dr. Genuardi said.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Primary care physicians, and especially pediatricians, should consider telling their patients about the long-term oral health problems associated with vaping.
A new study found that patients who use vapes were at a higher risk of developing tooth decay and periodontal disease.
Vapes were introduced to the U.S. market in 2006 as an alternative to conventional cigarettes and have become widely popular among youth. According to a 2022 survey from the U.S. Centers for Disease Control and Prevention, 2.55 million middle and high school students in this country reported using the devices in the previous 30 days.
The new study, published in the Journal of the American Dental Association, expands on an initial case series published in 2020 of patients who reported use of vapes and who had severe dental decay. Karina Irusa, BDS, assistant professor of comprehensive care at Tufts University, Boston, and lead author of the case series, wanted to investigate whether her initial findings would apply to a large population of vape users.
For the new study, Dr. Irusa and colleagues collected data on 13,216 patients aged 16-40 who attended Tufts dental clinics between 2019 and 2021. All patients had received a diagnosis of tooth decay, had a tooth decay risk assessment on record, and had answered “yes” or “no” to use of vapes in a health history questionnaire.
Patients had records on file of varying types of dental lesions, cavities filled within the previous 3 years, heavy plaque on teeth, inadequate brushing and flushing, and a self-report of recreational drug use and frequent snacking. If patients had these factors on their file, they were at high risk of developing decay that leads to cavities.
The study found that 79% of patients who responded “yes” to being a current user of vapes were at high risk for dental decay, compared with 60% of those who did not report using the devices.
Materials in the vaping liquids further cause an inflammatory response that disrupts an individual’s internal microbiome, according to numerous studies.
“All the ingredients of vaping are surely a recipe for overgrowth of cavities causing bacteria,” said Jennifer Genuardi, MD, an internist and pediatrician at federally qualified community health center Urban Health Plan, in New York, who was not involved in the study.
Dr. Irusa said information on patient’s vaping habits should be included in routine dental and medical history questionnaires as part of their overall electronic health record.
“Decay in its severe form not only affects one’s ability to eat but affects facial aesthetics and self-esteem as well,” Dr. Irusa said.
Dr. Genuardi called the findings unsurprising.
“We are learning daily more and more about the dangers of vaping,” Dr. Genuardi said. “There’s a focus of today’s research on the effect of actions on our microbiome and the subsequent effects on our health.”
Dr. Genuardi also said many of her teenage patients do not enjoy dental visits or having cavities filled, which could serve as a useful deterrent to vaping for a demographic that has been targeted with marketing from vape manufacturers.
“Cavity formation and the experience of having cavities filled is an experience teens can identify with, so this to me seems like perhaps an even more effective angle to try to curb this unhealthy behavior of vaping,” Dr. Genuardi said.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF THE AMERICAN DENTAL ASSOCIATION