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Baked milk immunotherapy may help children with cow’s milk allergy
, new research suggests.
The small, ongoing clinical trial has enabled some participants – all of whom reacted to less than a tablespoon of baked milk at baseline – to begin incorporating baked milk products into everyday diets and to eat in restaurants with less fear of allergic reactions, reported study author Jennifer Dantzer, MD, MHS, assistant professor of pediatrics in the division of pediatric allergy, immunology, and rheumatology at Johns Hopkins University in Baltimore.
Cow’s milk is the most common food allergy in young children, and “for many, it’s a constant stressor that’s always there,” Dr. Dantzer said in an interview. “For a lot of families, this impacts where they eat out, if they eat out, and sometimes where they vacation, or a lot of the social activities they do.
“This was a unique group of kids with a very severe milk phenotype who were reactive to teeny doses and may not have qualified or done well with other types of oral immunotherapy,” she added. “Using a modified allergen – baked milk – seems to work. But for now, we think this is something that still needs further research before it’s ready for a clinical setting.”
The study, for which 24-month unblinded results are being tallied, was recently published in the Journal of Allergy and Clinical Immunology .
About 2%-3% of preschool-age children are affected by cow’s milk allergy. Children often outgrow it, but for about 20% of children, it persists into adolescence and adulthood. The only current management approaches are avoidance and emergency medications to treat reactions.
But for those with severe milk allergy who react to even trace amounts of milk in any form, the now-routine clinical practice of introducing baked milk isn’t an option, Dr. Dantzer said. The new trial stood out from prior research by using lower starting doses and a more gradual dose escalation of extensively heated milk to determine if oral immunotherapy could be safer but still effective.
Dr. Dantzer and her team randomly assigned 30 participants (aged 3-18 years) into two blinded groups. For 12 months, one group received baked milk oral immunotherapy (BMOIT), and the other a placebo consisting of tapioca flour. At baseline, for all participants, the milk skin prick test wheal diameter was ≥ 3 mm, and the cow’s milk immunoglobulin E (IgE) level was > 5 kU/L. All the children experienced positive dose-limiting reactions to < 1 tablespoon of baked milk protein but could tolerate at least 3 mg on initial dose escalation.
Measured doses of baked milk and placebo powders were supplied to participants for all doses consumed at home. Participants were given instructions on how to prepare it in cupcake or muffin batter. Over 12 months, doses were gradually increased to a maximum cumulative dose of 4,044 mg baked milk protein, or approximately a half tablespoon.
Researchers collected blood samples for immune studies, and participants or their parents completed quality-of-life questionnaires that asked about food anxiety, social and dietary limitations, emotional impact, risk for accidental ingestion, and allergen avoidance.
Fourteen of 15 participants (93%) in the BMOIT group reached the goal-maintenance dose of 2,000 mg of baked milk protein (about a quarter tablespoon). Of those who completed the 12-month challenge, 11 of 14 (79%) in the BMOIT group tolerated 4,000 mg of baked milk protein, compared to none in the placebo group.
“We anticipated that by starting with really small amounts, we would be able to build up the amount of baked milk these kids could tolerate,” Dr. Dantzer said. “We were very pleased by how many could reach the maximal dose at the end of the first year. Once we get the results of the second year, that will provide a lot of additional detail about how this translates into unheated milk amounts they can tolerate and introduce into their diet at home.”
No significant changes were found in IgE levels over time in either study group. Most in the BMOIT group reported improvement in at least one quality-of-life domain, while more in the placebo group reported improvements in only the emotional impact domain.
Adverse events such as gastrointestinal side effects occurred in both groups of participants, but the vast majority of events were mild, Dr. Dantzer said. Fewer than 1% of dosing-related reactions were severe. Four participants required epinephrine.
“This highlights how this needs to be done by someone comfortable and trained, and not by a family at home on their own,” Dr. Dantzer said. “But potentially in the future, this concept of using a modified allergen could be applied to more kids with milk allergy.”
A Montreal-based pediatric allergy specialist who was not involved in the study said the results weren’t surprising. “We’ve known for a good while that the allergenic proteins found in certain foods, or caused by milk in this context, are influenced by the way in which food is processed,” said Christine McCusker, MD, associate professor of pediatrics and director of the division of pediatric allergy, immunology, and dermatology at Montreal Children’s Hospital at McGill University Health Center.
But “having this relatively definitive data that supports what you’re suggesting to patients is obviously the way to optimize your management,” Dr. McCusker said in an interview. “These types of studies are important steps, especially in this age of increased food allergies where many of these things can be dealt with in very young children before their immune systems are fixed.”
Dr. Dantzer and Dr. McCusker agreed that the small size of the study was a limitation, though “waiting for more participants means you don’t always get information out there in a timely manner,” Dr. McCusker said.
She said additional research should focus on preidentifying which children may be prone to severe, lasting food allergies. “If you have a milk allergy that will stay with you the rest of your life and we could maybe modify that outcome with early, targeted intervention, that would be the nirvana of the field,” Dr. McCusker said.
Dr. Dantzer said her research “showed us that oral immunotherapy is an option, but not a perfect option.
“We still need to keep working on other alternatives that can be even safer and potentially work better,” she added.
The study was supported by the Myra Reinhard Family Foundation. Dr. Dantzer and Dr. McCusker report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
The small, ongoing clinical trial has enabled some participants – all of whom reacted to less than a tablespoon of baked milk at baseline – to begin incorporating baked milk products into everyday diets and to eat in restaurants with less fear of allergic reactions, reported study author Jennifer Dantzer, MD, MHS, assistant professor of pediatrics in the division of pediatric allergy, immunology, and rheumatology at Johns Hopkins University in Baltimore.
Cow’s milk is the most common food allergy in young children, and “for many, it’s a constant stressor that’s always there,” Dr. Dantzer said in an interview. “For a lot of families, this impacts where they eat out, if they eat out, and sometimes where they vacation, or a lot of the social activities they do.
“This was a unique group of kids with a very severe milk phenotype who were reactive to teeny doses and may not have qualified or done well with other types of oral immunotherapy,” she added. “Using a modified allergen – baked milk – seems to work. But for now, we think this is something that still needs further research before it’s ready for a clinical setting.”
The study, for which 24-month unblinded results are being tallied, was recently published in the Journal of Allergy and Clinical Immunology .
About 2%-3% of preschool-age children are affected by cow’s milk allergy. Children often outgrow it, but for about 20% of children, it persists into adolescence and adulthood. The only current management approaches are avoidance and emergency medications to treat reactions.
But for those with severe milk allergy who react to even trace amounts of milk in any form, the now-routine clinical practice of introducing baked milk isn’t an option, Dr. Dantzer said. The new trial stood out from prior research by using lower starting doses and a more gradual dose escalation of extensively heated milk to determine if oral immunotherapy could be safer but still effective.
Dr. Dantzer and her team randomly assigned 30 participants (aged 3-18 years) into two blinded groups. For 12 months, one group received baked milk oral immunotherapy (BMOIT), and the other a placebo consisting of tapioca flour. At baseline, for all participants, the milk skin prick test wheal diameter was ≥ 3 mm, and the cow’s milk immunoglobulin E (IgE) level was > 5 kU/L. All the children experienced positive dose-limiting reactions to < 1 tablespoon of baked milk protein but could tolerate at least 3 mg on initial dose escalation.
Measured doses of baked milk and placebo powders were supplied to participants for all doses consumed at home. Participants were given instructions on how to prepare it in cupcake or muffin batter. Over 12 months, doses were gradually increased to a maximum cumulative dose of 4,044 mg baked milk protein, or approximately a half tablespoon.
Researchers collected blood samples for immune studies, and participants or their parents completed quality-of-life questionnaires that asked about food anxiety, social and dietary limitations, emotional impact, risk for accidental ingestion, and allergen avoidance.
Fourteen of 15 participants (93%) in the BMOIT group reached the goal-maintenance dose of 2,000 mg of baked milk protein (about a quarter tablespoon). Of those who completed the 12-month challenge, 11 of 14 (79%) in the BMOIT group tolerated 4,000 mg of baked milk protein, compared to none in the placebo group.
“We anticipated that by starting with really small amounts, we would be able to build up the amount of baked milk these kids could tolerate,” Dr. Dantzer said. “We were very pleased by how many could reach the maximal dose at the end of the first year. Once we get the results of the second year, that will provide a lot of additional detail about how this translates into unheated milk amounts they can tolerate and introduce into their diet at home.”
No significant changes were found in IgE levels over time in either study group. Most in the BMOIT group reported improvement in at least one quality-of-life domain, while more in the placebo group reported improvements in only the emotional impact domain.
Adverse events such as gastrointestinal side effects occurred in both groups of participants, but the vast majority of events were mild, Dr. Dantzer said. Fewer than 1% of dosing-related reactions were severe. Four participants required epinephrine.
“This highlights how this needs to be done by someone comfortable and trained, and not by a family at home on their own,” Dr. Dantzer said. “But potentially in the future, this concept of using a modified allergen could be applied to more kids with milk allergy.”
A Montreal-based pediatric allergy specialist who was not involved in the study said the results weren’t surprising. “We’ve known for a good while that the allergenic proteins found in certain foods, or caused by milk in this context, are influenced by the way in which food is processed,” said Christine McCusker, MD, associate professor of pediatrics and director of the division of pediatric allergy, immunology, and dermatology at Montreal Children’s Hospital at McGill University Health Center.
But “having this relatively definitive data that supports what you’re suggesting to patients is obviously the way to optimize your management,” Dr. McCusker said in an interview. “These types of studies are important steps, especially in this age of increased food allergies where many of these things can be dealt with in very young children before their immune systems are fixed.”
Dr. Dantzer and Dr. McCusker agreed that the small size of the study was a limitation, though “waiting for more participants means you don’t always get information out there in a timely manner,” Dr. McCusker said.
She said additional research should focus on preidentifying which children may be prone to severe, lasting food allergies. “If you have a milk allergy that will stay with you the rest of your life and we could maybe modify that outcome with early, targeted intervention, that would be the nirvana of the field,” Dr. McCusker said.
Dr. Dantzer said her research “showed us that oral immunotherapy is an option, but not a perfect option.
“We still need to keep working on other alternatives that can be even safer and potentially work better,” she added.
The study was supported by the Myra Reinhard Family Foundation. Dr. Dantzer and Dr. McCusker report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
The small, ongoing clinical trial has enabled some participants – all of whom reacted to less than a tablespoon of baked milk at baseline – to begin incorporating baked milk products into everyday diets and to eat in restaurants with less fear of allergic reactions, reported study author Jennifer Dantzer, MD, MHS, assistant professor of pediatrics in the division of pediatric allergy, immunology, and rheumatology at Johns Hopkins University in Baltimore.
Cow’s milk is the most common food allergy in young children, and “for many, it’s a constant stressor that’s always there,” Dr. Dantzer said in an interview. “For a lot of families, this impacts where they eat out, if they eat out, and sometimes where they vacation, or a lot of the social activities they do.
“This was a unique group of kids with a very severe milk phenotype who were reactive to teeny doses and may not have qualified or done well with other types of oral immunotherapy,” she added. “Using a modified allergen – baked milk – seems to work. But for now, we think this is something that still needs further research before it’s ready for a clinical setting.”
The study, for which 24-month unblinded results are being tallied, was recently published in the Journal of Allergy and Clinical Immunology .
About 2%-3% of preschool-age children are affected by cow’s milk allergy. Children often outgrow it, but for about 20% of children, it persists into adolescence and adulthood. The only current management approaches are avoidance and emergency medications to treat reactions.
But for those with severe milk allergy who react to even trace amounts of milk in any form, the now-routine clinical practice of introducing baked milk isn’t an option, Dr. Dantzer said. The new trial stood out from prior research by using lower starting doses and a more gradual dose escalation of extensively heated milk to determine if oral immunotherapy could be safer but still effective.
Dr. Dantzer and her team randomly assigned 30 participants (aged 3-18 years) into two blinded groups. For 12 months, one group received baked milk oral immunotherapy (BMOIT), and the other a placebo consisting of tapioca flour. At baseline, for all participants, the milk skin prick test wheal diameter was ≥ 3 mm, and the cow’s milk immunoglobulin E (IgE) level was > 5 kU/L. All the children experienced positive dose-limiting reactions to < 1 tablespoon of baked milk protein but could tolerate at least 3 mg on initial dose escalation.
Measured doses of baked milk and placebo powders were supplied to participants for all doses consumed at home. Participants were given instructions on how to prepare it in cupcake or muffin batter. Over 12 months, doses were gradually increased to a maximum cumulative dose of 4,044 mg baked milk protein, or approximately a half tablespoon.
Researchers collected blood samples for immune studies, and participants or their parents completed quality-of-life questionnaires that asked about food anxiety, social and dietary limitations, emotional impact, risk for accidental ingestion, and allergen avoidance.
Fourteen of 15 participants (93%) in the BMOIT group reached the goal-maintenance dose of 2,000 mg of baked milk protein (about a quarter tablespoon). Of those who completed the 12-month challenge, 11 of 14 (79%) in the BMOIT group tolerated 4,000 mg of baked milk protein, compared to none in the placebo group.
“We anticipated that by starting with really small amounts, we would be able to build up the amount of baked milk these kids could tolerate,” Dr. Dantzer said. “We were very pleased by how many could reach the maximal dose at the end of the first year. Once we get the results of the second year, that will provide a lot of additional detail about how this translates into unheated milk amounts they can tolerate and introduce into their diet at home.”
No significant changes were found in IgE levels over time in either study group. Most in the BMOIT group reported improvement in at least one quality-of-life domain, while more in the placebo group reported improvements in only the emotional impact domain.
Adverse events such as gastrointestinal side effects occurred in both groups of participants, but the vast majority of events were mild, Dr. Dantzer said. Fewer than 1% of dosing-related reactions were severe. Four participants required epinephrine.
“This highlights how this needs to be done by someone comfortable and trained, and not by a family at home on their own,” Dr. Dantzer said. “But potentially in the future, this concept of using a modified allergen could be applied to more kids with milk allergy.”
A Montreal-based pediatric allergy specialist who was not involved in the study said the results weren’t surprising. “We’ve known for a good while that the allergenic proteins found in certain foods, or caused by milk in this context, are influenced by the way in which food is processed,” said Christine McCusker, MD, associate professor of pediatrics and director of the division of pediatric allergy, immunology, and dermatology at Montreal Children’s Hospital at McGill University Health Center.
But “having this relatively definitive data that supports what you’re suggesting to patients is obviously the way to optimize your management,” Dr. McCusker said in an interview. “These types of studies are important steps, especially in this age of increased food allergies where many of these things can be dealt with in very young children before their immune systems are fixed.”
Dr. Dantzer and Dr. McCusker agreed that the small size of the study was a limitation, though “waiting for more participants means you don’t always get information out there in a timely manner,” Dr. McCusker said.
She said additional research should focus on preidentifying which children may be prone to severe, lasting food allergies. “If you have a milk allergy that will stay with you the rest of your life and we could maybe modify that outcome with early, targeted intervention, that would be the nirvana of the field,” Dr. McCusker said.
Dr. Dantzer said her research “showed us that oral immunotherapy is an option, but not a perfect option.
“We still need to keep working on other alternatives that can be even safer and potentially work better,” she added.
The study was supported by the Myra Reinhard Family Foundation. Dr. Dantzer and Dr. McCusker report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Fast foods contain endocrine-disrupting chemicals
, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.
The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.
“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.
“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.
A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.
Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.
“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”
The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
Fast foods containing meat had highest concentrations of chemicals
Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.
Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.
The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).
Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.
“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.
The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.
Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.
“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”
Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.
“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”
The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.
The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.
“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.
“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.
A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.
Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.
“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”
The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
Fast foods containing meat had highest concentrations of chemicals
Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.
Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.
The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).
Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.
“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.
The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.
Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.
“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”
Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.
“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”
The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.
The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.
“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.
“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.
A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.
Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.
“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”
The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
Fast foods containing meat had highest concentrations of chemicals
Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.
Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.
The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).
Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.
“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.
The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.
Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.
“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”
Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.
“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”
The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF EXPOSURE SCIENCE & ENVIRONMENTAL EPIDEMIOLOGY
Long COVID could spell kidney troubles down the line
Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.
The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.
Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.
The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.
“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”
Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.
Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
COVID-19 survivors more likely to have kidney damage than controls
“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”
This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.
“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.
Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.
Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.
Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
If your patient had COVID-19, ‘it’s reasonable to check kidney function’
“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.
“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.
If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.
“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”
Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.
“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.
The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.
The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.
“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.
“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.
The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.
The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.
Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.
The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.
“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”
Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.
Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
COVID-19 survivors more likely to have kidney damage than controls
“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”
This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.
“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.
Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.
Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.
Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
If your patient had COVID-19, ‘it’s reasonable to check kidney function’
“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.
“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.
If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.
“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”
Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.
“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.
The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.
The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.
“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.
“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.
The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.
The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.
Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.
The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.
“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”
Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.
Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
COVID-19 survivors more likely to have kidney damage than controls
“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”
This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.
“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.
Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.
Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.
Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
If your patient had COVID-19, ‘it’s reasonable to check kidney function’
“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.
“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.
If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.
“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”
Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.
“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.
The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.
The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.
“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.
“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.
The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When should patients with kidney disease receive nephrology referral?
And combining the two methods – predicted kidney failure risk with lab values – will lead to better patient outcomes by pinpointing CKD patients who most need specialty care, said study author Vishal Duggal, MD, who was a postdoctoral fellow in medical informatics at the Veterans Affairs Palo Alto (Calif.) Health Care System while conducting the research.
“We hope this can provide guidance to primary care physicians and nephrologists to give context for their decision-making,” Dr. Duggal told this news organization.
The VA is the largest provider of CKD care in the United States, developing clinical practice guidelines for CKD management that include suggested indications for nephrology referral based on laboratory values. Laboratory values that are typically used to guide referral include estimated glomerular filtration rate (eGFR) and its rate of decline per year, as well as heavy proteinuria in patients with and without diabetes.
Dr. Duggal and colleagues – who published their findings in the American Journal of Kidney Diseases – conducted a retrospective analysis of nearly 400,000 veterans with CKD over a yearlong period to determine if referral volume would change if it was based on the estimated risk for kidney failure, rather than solely using laboratory values.
They also estimated the potential volume of nephrology referrals based on a combination of both estimated risk for kidney failure and laboratory data.
Kidney failure risk was calculated using an electronic clinical decision support tool, called Kidney Failure Risk Equation incorporating age, eGFR, gender, and urine albumin-to-creatinine ratio.
Targeting fewer patients to specialty care
Among all participants with CKD not already receiving nephrology care, more than 150,000 (41.5%) had a urine albumin or protein measurement leading to computable risk for end-stage kidney disease.
More than 66,200 patients met actual laboratory indications for referral but had not previously seen a nephrologist. Among these patients, 11,752 (17.7%) were referred to nephrology in the following year, and all had a median 2-year predicted risk for kidney failure of 1.5%.
Referred patients were more likely to meet several potential referral criteria, especially eGFR less than 30 mL/min per 1.73 m2 and heavy proteinuria. Those with heavy proteinuria with diabetes, or the eGFR indication, had the highest predicted risk for kidney failure at 2 years, at 10% and 7.1% respectively.
Boosting referral volume can be problematic if patients aren’t prioritized by need, Dr. Duggal said, noting that many reasons explain why fewer than one in five CKD patients meeting lab indications for referral aren’t actually referred.
This can include patient preference, he noted: “Kidney disease is a disease of aging, and some patients don’t want to see a specialist or escalate their care.”
“Also, not everyone who has CKD is recommended to see a nephrologist, since primary care physicians do manage a lot of CKD as well.”
Basing referral on predicted kidney failure risk alone, a 2-year risk threshold of at least 1%, would identify a comparable number of patients (n = 72,948) as laboratory-based criteria, the team found, although they note that the patients identified using the KFRE tool would be at higher risk than those identified by lab values alone.
But when they combined the two – a minimum kidney failure risk of at least 1% over 2 years being applied to all new patients meeting lab-based referral indications, those pinpointed for nephrology referral dropped by 42.3%, from 66,276 to an estimated 38,229 patients.
“The current guidelines that just incorporate lab values identify a significant number of patients who are at low risk of developing end-stage kidney disease (ESKD), so incorporating kidney failure risk into current guidelines would target fewer patients to get to specialty care,” Dr. Duggal explained.
KFRE tool can be found online
Dr. Duggal emphasized that his findings do not change nephrology referral guidelines, but said physicians can find the KFRE tool online and use it to supplement their decision-making about a patient’s care.
“Further incorporating this [kidney failure] risk into referral practices might highlight a patient at extremely high risk who would benefit more from an interdisciplinary care team,” he said.
This could include, for example, a nutritionist to help the patient modify his or her diet. “Getting that kind of teaching process in place for a patient might be highly valuable,” he added.
Dr. Duggal disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
And combining the two methods – predicted kidney failure risk with lab values – will lead to better patient outcomes by pinpointing CKD patients who most need specialty care, said study author Vishal Duggal, MD, who was a postdoctoral fellow in medical informatics at the Veterans Affairs Palo Alto (Calif.) Health Care System while conducting the research.
“We hope this can provide guidance to primary care physicians and nephrologists to give context for their decision-making,” Dr. Duggal told this news organization.
The VA is the largest provider of CKD care in the United States, developing clinical practice guidelines for CKD management that include suggested indications for nephrology referral based on laboratory values. Laboratory values that are typically used to guide referral include estimated glomerular filtration rate (eGFR) and its rate of decline per year, as well as heavy proteinuria in patients with and without diabetes.
Dr. Duggal and colleagues – who published their findings in the American Journal of Kidney Diseases – conducted a retrospective analysis of nearly 400,000 veterans with CKD over a yearlong period to determine if referral volume would change if it was based on the estimated risk for kidney failure, rather than solely using laboratory values.
They also estimated the potential volume of nephrology referrals based on a combination of both estimated risk for kidney failure and laboratory data.
Kidney failure risk was calculated using an electronic clinical decision support tool, called Kidney Failure Risk Equation incorporating age, eGFR, gender, and urine albumin-to-creatinine ratio.
Targeting fewer patients to specialty care
Among all participants with CKD not already receiving nephrology care, more than 150,000 (41.5%) had a urine albumin or protein measurement leading to computable risk for end-stage kidney disease.
More than 66,200 patients met actual laboratory indications for referral but had not previously seen a nephrologist. Among these patients, 11,752 (17.7%) were referred to nephrology in the following year, and all had a median 2-year predicted risk for kidney failure of 1.5%.
Referred patients were more likely to meet several potential referral criteria, especially eGFR less than 30 mL/min per 1.73 m2 and heavy proteinuria. Those with heavy proteinuria with diabetes, or the eGFR indication, had the highest predicted risk for kidney failure at 2 years, at 10% and 7.1% respectively.
Boosting referral volume can be problematic if patients aren’t prioritized by need, Dr. Duggal said, noting that many reasons explain why fewer than one in five CKD patients meeting lab indications for referral aren’t actually referred.
This can include patient preference, he noted: “Kidney disease is a disease of aging, and some patients don’t want to see a specialist or escalate their care.”
“Also, not everyone who has CKD is recommended to see a nephrologist, since primary care physicians do manage a lot of CKD as well.”
Basing referral on predicted kidney failure risk alone, a 2-year risk threshold of at least 1%, would identify a comparable number of patients (n = 72,948) as laboratory-based criteria, the team found, although they note that the patients identified using the KFRE tool would be at higher risk than those identified by lab values alone.
But when they combined the two – a minimum kidney failure risk of at least 1% over 2 years being applied to all new patients meeting lab-based referral indications, those pinpointed for nephrology referral dropped by 42.3%, from 66,276 to an estimated 38,229 patients.
“The current guidelines that just incorporate lab values identify a significant number of patients who are at low risk of developing end-stage kidney disease (ESKD), so incorporating kidney failure risk into current guidelines would target fewer patients to get to specialty care,” Dr. Duggal explained.
KFRE tool can be found online
Dr. Duggal emphasized that his findings do not change nephrology referral guidelines, but said physicians can find the KFRE tool online and use it to supplement their decision-making about a patient’s care.
“Further incorporating this [kidney failure] risk into referral practices might highlight a patient at extremely high risk who would benefit more from an interdisciplinary care team,” he said.
This could include, for example, a nutritionist to help the patient modify his or her diet. “Getting that kind of teaching process in place for a patient might be highly valuable,” he added.
Dr. Duggal disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
And combining the two methods – predicted kidney failure risk with lab values – will lead to better patient outcomes by pinpointing CKD patients who most need specialty care, said study author Vishal Duggal, MD, who was a postdoctoral fellow in medical informatics at the Veterans Affairs Palo Alto (Calif.) Health Care System while conducting the research.
“We hope this can provide guidance to primary care physicians and nephrologists to give context for their decision-making,” Dr. Duggal told this news organization.
The VA is the largest provider of CKD care in the United States, developing clinical practice guidelines for CKD management that include suggested indications for nephrology referral based on laboratory values. Laboratory values that are typically used to guide referral include estimated glomerular filtration rate (eGFR) and its rate of decline per year, as well as heavy proteinuria in patients with and without diabetes.
Dr. Duggal and colleagues – who published their findings in the American Journal of Kidney Diseases – conducted a retrospective analysis of nearly 400,000 veterans with CKD over a yearlong period to determine if referral volume would change if it was based on the estimated risk for kidney failure, rather than solely using laboratory values.
They also estimated the potential volume of nephrology referrals based on a combination of both estimated risk for kidney failure and laboratory data.
Kidney failure risk was calculated using an electronic clinical decision support tool, called Kidney Failure Risk Equation incorporating age, eGFR, gender, and urine albumin-to-creatinine ratio.
Targeting fewer patients to specialty care
Among all participants with CKD not already receiving nephrology care, more than 150,000 (41.5%) had a urine albumin or protein measurement leading to computable risk for end-stage kidney disease.
More than 66,200 patients met actual laboratory indications for referral but had not previously seen a nephrologist. Among these patients, 11,752 (17.7%) were referred to nephrology in the following year, and all had a median 2-year predicted risk for kidney failure of 1.5%.
Referred patients were more likely to meet several potential referral criteria, especially eGFR less than 30 mL/min per 1.73 m2 and heavy proteinuria. Those with heavy proteinuria with diabetes, or the eGFR indication, had the highest predicted risk for kidney failure at 2 years, at 10% and 7.1% respectively.
Boosting referral volume can be problematic if patients aren’t prioritized by need, Dr. Duggal said, noting that many reasons explain why fewer than one in five CKD patients meeting lab indications for referral aren’t actually referred.
This can include patient preference, he noted: “Kidney disease is a disease of aging, and some patients don’t want to see a specialist or escalate their care.”
“Also, not everyone who has CKD is recommended to see a nephrologist, since primary care physicians do manage a lot of CKD as well.”
Basing referral on predicted kidney failure risk alone, a 2-year risk threshold of at least 1%, would identify a comparable number of patients (n = 72,948) as laboratory-based criteria, the team found, although they note that the patients identified using the KFRE tool would be at higher risk than those identified by lab values alone.
But when they combined the two – a minimum kidney failure risk of at least 1% over 2 years being applied to all new patients meeting lab-based referral indications, those pinpointed for nephrology referral dropped by 42.3%, from 66,276 to an estimated 38,229 patients.
“The current guidelines that just incorporate lab values identify a significant number of patients who are at low risk of developing end-stage kidney disease (ESKD), so incorporating kidney failure risk into current guidelines would target fewer patients to get to specialty care,” Dr. Duggal explained.
KFRE tool can be found online
Dr. Duggal emphasized that his findings do not change nephrology referral guidelines, but said physicians can find the KFRE tool online and use it to supplement their decision-making about a patient’s care.
“Further incorporating this [kidney failure] risk into referral practices might highlight a patient at extremely high risk who would benefit more from an interdisciplinary care team,” he said.
This could include, for example, a nutritionist to help the patient modify his or her diet. “Getting that kind of teaching process in place for a patient might be highly valuable,” he added.
Dr. Duggal disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
U.K. variant spreading in the U.S. as COVID mutations raise stakes
The U.K.’s B117 variant is circulating in at least 24 states, according to new data from the Centers for Disease Control and Prevention COVID-19 variant surveillance. The CDC projects that the U.K. variant will become the dominant strain in the United States by March.
From any vantage point, the United Kingdom appears to be in the crosshairs of COVID-19: Weeks after a new, highly contagious variant emerged that fueled a surge in cases and fresh lockdowns, the United Kingdom was revealed to have the world’s highest coronavirus death rate.
But the United Kingdom also has a not-so-secret weapon of its own: A genomic sequencing program widely believed to be the most coordinated and advanced any nation has forged. In the vise grip of the virus, the Brits have gleaned key insights into the behavior and consequences of SARS-CoV-2.
But B117 is also notable for what it is missing: In this case, producing a negative result on certain polymerase chain reaction (PCR) tests in the spike protein, or S-gene.
One of the S-gene mutations specific to the variant deletes two amino acids, causing that portion of the PCR test to show up negative. The coincidental finding known as an S-gene target failure has become an integral proxy to help track where and when the variant is spreading in the United Kingdom, where about 5% of samples from COVID-19–infected patients are sequenced, said Sharon Peacock, PhD, executive director and chair of the COVID-19 Genomics U.K. Consortium.
That same tactic could prove valuable to clinicians similarly overwhelmed with cases and deaths but lacking high-level sequencing information on the virus, Dr. Peacock said in an interview. A British report released Friday stated that there is a “realistic possibility” that the variant has a higher death rate than other cases of SARS-CoV-2.
“In this particular variant, a deletion in the genome leads to one part of the diagnostic test failing,” Dr. Peacock explained. “Several targets are positive, but this is negative. In the U.K., this has been used as a surrogate marker.”
Targeting an invisible adversary
B117 is not the only variant that produces this result, Dr. Peacock cautioned, “but in screening for it, you can have this in mind.”
“Since the U.K. is sequencing about 5% of the cases they detect, this gives them really important clues about what’s happening there,” said Anderson Brito, PhD, a virologist and postdoctoral researcher at Yale University, New Haven, Conn., where investigators are creating custom PCR tests to detect the B117 variant.
Dr. Brito, who lived in the United Kingdom for 4 years while studying for his doctorate at Imperial College London, said a “major advantage” is the more unified process to collect and sequence samples. Crucial information – including the date and place of collection – comes with each sample, which fuels not only sequencing, but an epidemiologic perspective.
“They’re not in the dark at all,” Dr. Brito said in an interview. “I think no other country in the world knows better which virus lineages are circulating.”
The CDC launched the SPHERES consortium in May 2020 to coordinate the sequencing of SARS-CoV-2 genomes across the United States.
But American genomic efforts are “not as centralized,” said Dr. Brito, whose lab detected the first two cases of the U.K. variant in Connecticut on Jan. 6. “We struggle to get samples, because they’re decentralized to a level where there’s little coordination between hospitals and research centers. They’re not as connected as in the U.K. If we just get a sample and it has no date of collection and no origin information, for example, it’s basically useless.”
Global genomic collaborations include GISAID, an international database where researchers share new genomes from various coronaviruses. As of mid-January, the United States had submitted about 68,000 sequences to GISAID, adding about 3,000 new samples every week and expecting even more from commercial labs in coming days, according to the CDC.
“The U.K. is definitely much more on top of looking for variants as they pop up,” said Gigi Gronvall, PhD, an immunologist and senior scholar at Johns Hopkins Center for Health Security in Baltimore. “The U.S. has now turned that up.”
Warning from British scientists to the world
Despite these genomic accomplishments, some British scientists said they have regrets too, wishing they’d known just how rapidly SARS-CoV-2 was actually spreading a year ago, when it hit western Europe.
That information was crucial not only for preventive efforts, but because viruses inevitably mutate faster the more people who are infected, said Igor Rudan, MD, PhD, director of the Center for Global Health Research at University of Edinburgh.
“Italy showed us just how fast it was spreading and how deadly it is for the very old and people with multiple comorbidities,” said Dr. Rudan, who also editor in chief of the Journal of Global Health. “We wish we knew it was spreading so fast, and we wish we knew the threshold of cases we could allow to be infected before the virus would mutate.”
More mutations mean more new strains of SARS-CoV-2, Dr. Rudan said in an interview. “We’ve reached that threshold now and will see more of these mutations.”
Despite its current struggles, the United Kingdom is reaching beyond tracking its new variant’s spread and trying to identify new mutations that might change the way the virus behaves.
Three features of any emerging variant are particularly important, Dr. Peacock explained: Is it more transmissible? Is it more lethal? And does it cut the ability of natural- or vaccine-induced immunity to protect people from infection?
“We need to sequence people coming to the hospital who are sicker,” said Dr. Peacock, also a professor of public health and microbiology at the University of Cambridge (England). “Also, if anyone has the infection after they’ve already been sick or had the vaccine, we really want to know what that looks like” genomically.
SARS-CoV-2 has already logged more than 4,000 mutations, Dr. Peacock said. But “knowing that viruses mutate all the time is not sufficient reason not to look. We really want to know if mutations lead to changes in amino acids, and if that can lead to changes in functionality.”
For the moment, however, experts say they’re relieved that the U.K. strain doesn’t seem able to evade COVID-19 vaccines or render them less effective.
“Even though mutations are common, those able to change the viral coding are rare,” Dr. Brito explained. If necessary, vaccines could be tweaked to replace the spike gene sequence “within a matter of weeks. We already do this for flu vaccines. Every year, we have to monitor variants of the virus circulating to develop a vaccine that covers most of them. If we end up having to do it for SARS-CoV-2, I would not be surprised.”
But variant-fueled increases in infections will require more people to be vaccinated before herd immunity can be achieved, Dr. Rudan warned. “If it spreads faster, we’ll need to vaccinate probably 85% of people versus 70% to reach herd immunity.”
One lesson the COVID-19 pandemic has driven home “is to always be on your guard about what happens next,” Dr. Peacock said. Although confident about the genomic efforts in the United Kingdom to date, she and her colleagues feel they’re still reaching for a complete understanding of the evolutionary changes of the virus.
“We’re ahead of the curve right now, but we want to get in front of the curve,” Dr. Peacock said. “It’s essential to get ahead of what might be around the corner because we don’t know how the virus is going to evolve.”
A version of this article first appeared on Medscape.com.
The U.K.’s B117 variant is circulating in at least 24 states, according to new data from the Centers for Disease Control and Prevention COVID-19 variant surveillance. The CDC projects that the U.K. variant will become the dominant strain in the United States by March.
From any vantage point, the United Kingdom appears to be in the crosshairs of COVID-19: Weeks after a new, highly contagious variant emerged that fueled a surge in cases and fresh lockdowns, the United Kingdom was revealed to have the world’s highest coronavirus death rate.
But the United Kingdom also has a not-so-secret weapon of its own: A genomic sequencing program widely believed to be the most coordinated and advanced any nation has forged. In the vise grip of the virus, the Brits have gleaned key insights into the behavior and consequences of SARS-CoV-2.
But B117 is also notable for what it is missing: In this case, producing a negative result on certain polymerase chain reaction (PCR) tests in the spike protein, or S-gene.
One of the S-gene mutations specific to the variant deletes two amino acids, causing that portion of the PCR test to show up negative. The coincidental finding known as an S-gene target failure has become an integral proxy to help track where and when the variant is spreading in the United Kingdom, where about 5% of samples from COVID-19–infected patients are sequenced, said Sharon Peacock, PhD, executive director and chair of the COVID-19 Genomics U.K. Consortium.
That same tactic could prove valuable to clinicians similarly overwhelmed with cases and deaths but lacking high-level sequencing information on the virus, Dr. Peacock said in an interview. A British report released Friday stated that there is a “realistic possibility” that the variant has a higher death rate than other cases of SARS-CoV-2.
“In this particular variant, a deletion in the genome leads to one part of the diagnostic test failing,” Dr. Peacock explained. “Several targets are positive, but this is negative. In the U.K., this has been used as a surrogate marker.”
Targeting an invisible adversary
B117 is not the only variant that produces this result, Dr. Peacock cautioned, “but in screening for it, you can have this in mind.”
“Since the U.K. is sequencing about 5% of the cases they detect, this gives them really important clues about what’s happening there,” said Anderson Brito, PhD, a virologist and postdoctoral researcher at Yale University, New Haven, Conn., where investigators are creating custom PCR tests to detect the B117 variant.
Dr. Brito, who lived in the United Kingdom for 4 years while studying for his doctorate at Imperial College London, said a “major advantage” is the more unified process to collect and sequence samples. Crucial information – including the date and place of collection – comes with each sample, which fuels not only sequencing, but an epidemiologic perspective.
“They’re not in the dark at all,” Dr. Brito said in an interview. “I think no other country in the world knows better which virus lineages are circulating.”
The CDC launched the SPHERES consortium in May 2020 to coordinate the sequencing of SARS-CoV-2 genomes across the United States.
But American genomic efforts are “not as centralized,” said Dr. Brito, whose lab detected the first two cases of the U.K. variant in Connecticut on Jan. 6. “We struggle to get samples, because they’re decentralized to a level where there’s little coordination between hospitals and research centers. They’re not as connected as in the U.K. If we just get a sample and it has no date of collection and no origin information, for example, it’s basically useless.”
Global genomic collaborations include GISAID, an international database where researchers share new genomes from various coronaviruses. As of mid-January, the United States had submitted about 68,000 sequences to GISAID, adding about 3,000 new samples every week and expecting even more from commercial labs in coming days, according to the CDC.
“The U.K. is definitely much more on top of looking for variants as they pop up,” said Gigi Gronvall, PhD, an immunologist and senior scholar at Johns Hopkins Center for Health Security in Baltimore. “The U.S. has now turned that up.”
Warning from British scientists to the world
Despite these genomic accomplishments, some British scientists said they have regrets too, wishing they’d known just how rapidly SARS-CoV-2 was actually spreading a year ago, when it hit western Europe.
That information was crucial not only for preventive efforts, but because viruses inevitably mutate faster the more people who are infected, said Igor Rudan, MD, PhD, director of the Center for Global Health Research at University of Edinburgh.
“Italy showed us just how fast it was spreading and how deadly it is for the very old and people with multiple comorbidities,” said Dr. Rudan, who also editor in chief of the Journal of Global Health. “We wish we knew it was spreading so fast, and we wish we knew the threshold of cases we could allow to be infected before the virus would mutate.”
More mutations mean more new strains of SARS-CoV-2, Dr. Rudan said in an interview. “We’ve reached that threshold now and will see more of these mutations.”
Despite its current struggles, the United Kingdom is reaching beyond tracking its new variant’s spread and trying to identify new mutations that might change the way the virus behaves.
Three features of any emerging variant are particularly important, Dr. Peacock explained: Is it more transmissible? Is it more lethal? And does it cut the ability of natural- or vaccine-induced immunity to protect people from infection?
“We need to sequence people coming to the hospital who are sicker,” said Dr. Peacock, also a professor of public health and microbiology at the University of Cambridge (England). “Also, if anyone has the infection after they’ve already been sick or had the vaccine, we really want to know what that looks like” genomically.
SARS-CoV-2 has already logged more than 4,000 mutations, Dr. Peacock said. But “knowing that viruses mutate all the time is not sufficient reason not to look. We really want to know if mutations lead to changes in amino acids, and if that can lead to changes in functionality.”
For the moment, however, experts say they’re relieved that the U.K. strain doesn’t seem able to evade COVID-19 vaccines or render them less effective.
“Even though mutations are common, those able to change the viral coding are rare,” Dr. Brito explained. If necessary, vaccines could be tweaked to replace the spike gene sequence “within a matter of weeks. We already do this for flu vaccines. Every year, we have to monitor variants of the virus circulating to develop a vaccine that covers most of them. If we end up having to do it for SARS-CoV-2, I would not be surprised.”
But variant-fueled increases in infections will require more people to be vaccinated before herd immunity can be achieved, Dr. Rudan warned. “If it spreads faster, we’ll need to vaccinate probably 85% of people versus 70% to reach herd immunity.”
One lesson the COVID-19 pandemic has driven home “is to always be on your guard about what happens next,” Dr. Peacock said. Although confident about the genomic efforts in the United Kingdom to date, she and her colleagues feel they’re still reaching for a complete understanding of the evolutionary changes of the virus.
“We’re ahead of the curve right now, but we want to get in front of the curve,” Dr. Peacock said. “It’s essential to get ahead of what might be around the corner because we don’t know how the virus is going to evolve.”
A version of this article first appeared on Medscape.com.
The U.K.’s B117 variant is circulating in at least 24 states, according to new data from the Centers for Disease Control and Prevention COVID-19 variant surveillance. The CDC projects that the U.K. variant will become the dominant strain in the United States by March.
From any vantage point, the United Kingdom appears to be in the crosshairs of COVID-19: Weeks after a new, highly contagious variant emerged that fueled a surge in cases and fresh lockdowns, the United Kingdom was revealed to have the world’s highest coronavirus death rate.
But the United Kingdom also has a not-so-secret weapon of its own: A genomic sequencing program widely believed to be the most coordinated and advanced any nation has forged. In the vise grip of the virus, the Brits have gleaned key insights into the behavior and consequences of SARS-CoV-2.
But B117 is also notable for what it is missing: In this case, producing a negative result on certain polymerase chain reaction (PCR) tests in the spike protein, or S-gene.
One of the S-gene mutations specific to the variant deletes two amino acids, causing that portion of the PCR test to show up negative. The coincidental finding known as an S-gene target failure has become an integral proxy to help track where and when the variant is spreading in the United Kingdom, where about 5% of samples from COVID-19–infected patients are sequenced, said Sharon Peacock, PhD, executive director and chair of the COVID-19 Genomics U.K. Consortium.
That same tactic could prove valuable to clinicians similarly overwhelmed with cases and deaths but lacking high-level sequencing information on the virus, Dr. Peacock said in an interview. A British report released Friday stated that there is a “realistic possibility” that the variant has a higher death rate than other cases of SARS-CoV-2.
“In this particular variant, a deletion in the genome leads to one part of the diagnostic test failing,” Dr. Peacock explained. “Several targets are positive, but this is negative. In the U.K., this has been used as a surrogate marker.”
Targeting an invisible adversary
B117 is not the only variant that produces this result, Dr. Peacock cautioned, “but in screening for it, you can have this in mind.”
“Since the U.K. is sequencing about 5% of the cases they detect, this gives them really important clues about what’s happening there,” said Anderson Brito, PhD, a virologist and postdoctoral researcher at Yale University, New Haven, Conn., where investigators are creating custom PCR tests to detect the B117 variant.
Dr. Brito, who lived in the United Kingdom for 4 years while studying for his doctorate at Imperial College London, said a “major advantage” is the more unified process to collect and sequence samples. Crucial information – including the date and place of collection – comes with each sample, which fuels not only sequencing, but an epidemiologic perspective.
“They’re not in the dark at all,” Dr. Brito said in an interview. “I think no other country in the world knows better which virus lineages are circulating.”
The CDC launched the SPHERES consortium in May 2020 to coordinate the sequencing of SARS-CoV-2 genomes across the United States.
But American genomic efforts are “not as centralized,” said Dr. Brito, whose lab detected the first two cases of the U.K. variant in Connecticut on Jan. 6. “We struggle to get samples, because they’re decentralized to a level where there’s little coordination between hospitals and research centers. They’re not as connected as in the U.K. If we just get a sample and it has no date of collection and no origin information, for example, it’s basically useless.”
Global genomic collaborations include GISAID, an international database where researchers share new genomes from various coronaviruses. As of mid-January, the United States had submitted about 68,000 sequences to GISAID, adding about 3,000 new samples every week and expecting even more from commercial labs in coming days, according to the CDC.
“The U.K. is definitely much more on top of looking for variants as they pop up,” said Gigi Gronvall, PhD, an immunologist and senior scholar at Johns Hopkins Center for Health Security in Baltimore. “The U.S. has now turned that up.”
Warning from British scientists to the world
Despite these genomic accomplishments, some British scientists said they have regrets too, wishing they’d known just how rapidly SARS-CoV-2 was actually spreading a year ago, when it hit western Europe.
That information was crucial not only for preventive efforts, but because viruses inevitably mutate faster the more people who are infected, said Igor Rudan, MD, PhD, director of the Center for Global Health Research at University of Edinburgh.
“Italy showed us just how fast it was spreading and how deadly it is for the very old and people with multiple comorbidities,” said Dr. Rudan, who also editor in chief of the Journal of Global Health. “We wish we knew it was spreading so fast, and we wish we knew the threshold of cases we could allow to be infected before the virus would mutate.”
More mutations mean more new strains of SARS-CoV-2, Dr. Rudan said in an interview. “We’ve reached that threshold now and will see more of these mutations.”
Despite its current struggles, the United Kingdom is reaching beyond tracking its new variant’s spread and trying to identify new mutations that might change the way the virus behaves.
Three features of any emerging variant are particularly important, Dr. Peacock explained: Is it more transmissible? Is it more lethal? And does it cut the ability of natural- or vaccine-induced immunity to protect people from infection?
“We need to sequence people coming to the hospital who are sicker,” said Dr. Peacock, also a professor of public health and microbiology at the University of Cambridge (England). “Also, if anyone has the infection after they’ve already been sick or had the vaccine, we really want to know what that looks like” genomically.
SARS-CoV-2 has already logged more than 4,000 mutations, Dr. Peacock said. But “knowing that viruses mutate all the time is not sufficient reason not to look. We really want to know if mutations lead to changes in amino acids, and if that can lead to changes in functionality.”
For the moment, however, experts say they’re relieved that the U.K. strain doesn’t seem able to evade COVID-19 vaccines or render them less effective.
“Even though mutations are common, those able to change the viral coding are rare,” Dr. Brito explained. If necessary, vaccines could be tweaked to replace the spike gene sequence “within a matter of weeks. We already do this for flu vaccines. Every year, we have to monitor variants of the virus circulating to develop a vaccine that covers most of them. If we end up having to do it for SARS-CoV-2, I would not be surprised.”
But variant-fueled increases in infections will require more people to be vaccinated before herd immunity can be achieved, Dr. Rudan warned. “If it spreads faster, we’ll need to vaccinate probably 85% of people versus 70% to reach herd immunity.”
One lesson the COVID-19 pandemic has driven home “is to always be on your guard about what happens next,” Dr. Peacock said. Although confident about the genomic efforts in the United Kingdom to date, she and her colleagues feel they’re still reaching for a complete understanding of the evolutionary changes of the virus.
“We’re ahead of the curve right now, but we want to get in front of the curve,” Dr. Peacock said. “It’s essential to get ahead of what might be around the corner because we don’t know how the virus is going to evolve.”
A version of this article first appeared on Medscape.com.
Birch bark derivative gel found effective for EB, in phase 3 study
A . The results come from the largest double-blind, randomized trial performed in this patient population.
More than 41% of EB target wounds that were treated with Oleogel-S10 healed within 45 days, compared with about 29% of target wounds treated with placebo, in the EASE phase 3 trial, conducted at 58 sites in 28 countries.
A group of rare genetic disorders, EB “is described as the worst disease you’ve never heard of,” explained lead investigator Dedee Murrell, MD, director of dermatology, St. George Hospital at the University of New South Wales, Sydney. “It starts in children and is like having burns that heal with scars, and no treatment has been approved for it” by the Food and Drug Administration.
“This is the first large clinical trial with placebo of a topical treatment that’s worked for this terrible disease,” Dr. Murrell said in an interview. She noted that standard EB treatment currently consists of applying nonstick dressings to wounds to protect skin from trauma and infection.
Dr. Murrell, who has focused her work on EB patients since 1990, presented the findings at the virtual annual Congress of the European Academy of Dermatology and Venereology.
The trial enrolled 223 patients (average age, 12 years, but ages ranged to 81 years) with three types of EB, including dystrophic and junctional EB and Kindler syndrome. For each participant, a target wound was selected for use as the primary efficacy endpoint. Those wounds had a partial thickness of between 10 cm2 and 50 cm2 and lasted between 21 days and 9 months. Patients were stratified into groups depending on type of EB and size of target wound.
Participants were randomly assigned to receive either Oleogel-S10 (n = 109) or placebo (n = 114). All applied the blinded-study gel to all their wounds at least every 4 days at the time dressings were changed.
The primary endpoint was the percentage of patients whose target wounds completely closed within 45 days. Key secondary endpoints included time to wound healing and percentage of target wounds that healed within 90 days of treatment; incidence and severity of target wound infection; change in total body wound burden, as measured by the Epidermolysis Bullosa Disease Activity and Scarring Index skin activity subscore; change in itching, as measured by the Itch Man Scale and the Leuven Itch Scale; and adverse events.
Nearly 92% of patients who were treated with Oleogel-S10 completed the double-blind phase of the trial, compared with nearly 87% who received placebo. As noted, the primary endpoint was met, with 41.3% of Oleogel-S10 patients achieving target wound closure within 45 days, compared with 28.9% of the patients who received placebo (P = .013).
But the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of Oleogel-S10 patients achieving wound closure vs. 43.9% of control patients.
Target-wound infection occurred in eight participants, including three who used Oleogel-S10 and five who received placebo; all moderate or severe infections occurred in patients who received placebo. Total wound burden was reduced to a greater extent among Oleogel-S10 patients by day 60, but there was no apparent difference at day 90.
Both treatment groups reported qualitative improvements in itch, with no significant differences between groups. The prevalence of adverse events was also similar between groups (Oleogel-S10, 81.7%; placebo, 80.7%). The most frequently reported adverse events among Oleogel-S10 patients, compared with patients who received placebo, were wound complications, pyrexia, wound infection, pruritus, and anemia; only 4.5% of adverse events were deemed severe.
Dr. Murrell said that, on the basis of the trial results, she expects the FDA to fast-track approval of Oleogel-S10, which contains triterpene extract and sunflower oil.
The gel is “a treatment patients will be able to put under their dressings, added to normal treatment, which will accelerate their wound healing, with no significant increase in any side effects,” she added.
Jemima Mellerio, MD, of St. Thomas’ Hospital in London who sees about 400 EB patients each year, agreed with Dr. Murrell that the results are “very exciting.” Dr. Mellerio was not involved in the study.
“Practicing dermatologists seeing people with EB will have something to offer that appears to speed up wound healing in chronic wounds,” Dr. Mellerio said in an interview. “It’s a positive option rather than just supportive treatment, something that makes a difference to the natural history of wounds.”
She said the trial’s biggest strength was including “such a large cohort of patients.
“It’s extremely difficult to do that kind of study, especially with a placebo-controlled arm and especially in a rare disease,” Dr. Mellerio said. “If you think about the product itself, it’s easy to apply, so it’s not particularly onerous for people to add to their daily regimen of dressings.”
The study was funded by Amryt Pharma. Dr. Murrell is an advisory board member for Amryt Pharma. Dr. Mellerio is a consultant for Amryt Pharma.
A version of this article originally appeared on Medscape.com.
A . The results come from the largest double-blind, randomized trial performed in this patient population.
More than 41% of EB target wounds that were treated with Oleogel-S10 healed within 45 days, compared with about 29% of target wounds treated with placebo, in the EASE phase 3 trial, conducted at 58 sites in 28 countries.
A group of rare genetic disorders, EB “is described as the worst disease you’ve never heard of,” explained lead investigator Dedee Murrell, MD, director of dermatology, St. George Hospital at the University of New South Wales, Sydney. “It starts in children and is like having burns that heal with scars, and no treatment has been approved for it” by the Food and Drug Administration.
“This is the first large clinical trial with placebo of a topical treatment that’s worked for this terrible disease,” Dr. Murrell said in an interview. She noted that standard EB treatment currently consists of applying nonstick dressings to wounds to protect skin from trauma and infection.
Dr. Murrell, who has focused her work on EB patients since 1990, presented the findings at the virtual annual Congress of the European Academy of Dermatology and Venereology.
The trial enrolled 223 patients (average age, 12 years, but ages ranged to 81 years) with three types of EB, including dystrophic and junctional EB and Kindler syndrome. For each participant, a target wound was selected for use as the primary efficacy endpoint. Those wounds had a partial thickness of between 10 cm2 and 50 cm2 and lasted between 21 days and 9 months. Patients were stratified into groups depending on type of EB and size of target wound.
Participants were randomly assigned to receive either Oleogel-S10 (n = 109) or placebo (n = 114). All applied the blinded-study gel to all their wounds at least every 4 days at the time dressings were changed.
The primary endpoint was the percentage of patients whose target wounds completely closed within 45 days. Key secondary endpoints included time to wound healing and percentage of target wounds that healed within 90 days of treatment; incidence and severity of target wound infection; change in total body wound burden, as measured by the Epidermolysis Bullosa Disease Activity and Scarring Index skin activity subscore; change in itching, as measured by the Itch Man Scale and the Leuven Itch Scale; and adverse events.
Nearly 92% of patients who were treated with Oleogel-S10 completed the double-blind phase of the trial, compared with nearly 87% who received placebo. As noted, the primary endpoint was met, with 41.3% of Oleogel-S10 patients achieving target wound closure within 45 days, compared with 28.9% of the patients who received placebo (P = .013).
But the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of Oleogel-S10 patients achieving wound closure vs. 43.9% of control patients.
Target-wound infection occurred in eight participants, including three who used Oleogel-S10 and five who received placebo; all moderate or severe infections occurred in patients who received placebo. Total wound burden was reduced to a greater extent among Oleogel-S10 patients by day 60, but there was no apparent difference at day 90.
Both treatment groups reported qualitative improvements in itch, with no significant differences between groups. The prevalence of adverse events was also similar between groups (Oleogel-S10, 81.7%; placebo, 80.7%). The most frequently reported adverse events among Oleogel-S10 patients, compared with patients who received placebo, were wound complications, pyrexia, wound infection, pruritus, and anemia; only 4.5% of adverse events were deemed severe.
Dr. Murrell said that, on the basis of the trial results, she expects the FDA to fast-track approval of Oleogel-S10, which contains triterpene extract and sunflower oil.
The gel is “a treatment patients will be able to put under their dressings, added to normal treatment, which will accelerate their wound healing, with no significant increase in any side effects,” she added.
Jemima Mellerio, MD, of St. Thomas’ Hospital in London who sees about 400 EB patients each year, agreed with Dr. Murrell that the results are “very exciting.” Dr. Mellerio was not involved in the study.
“Practicing dermatologists seeing people with EB will have something to offer that appears to speed up wound healing in chronic wounds,” Dr. Mellerio said in an interview. “It’s a positive option rather than just supportive treatment, something that makes a difference to the natural history of wounds.”
She said the trial’s biggest strength was including “such a large cohort of patients.
“It’s extremely difficult to do that kind of study, especially with a placebo-controlled arm and especially in a rare disease,” Dr. Mellerio said. “If you think about the product itself, it’s easy to apply, so it’s not particularly onerous for people to add to their daily regimen of dressings.”
The study was funded by Amryt Pharma. Dr. Murrell is an advisory board member for Amryt Pharma. Dr. Mellerio is a consultant for Amryt Pharma.
A version of this article originally appeared on Medscape.com.
A . The results come from the largest double-blind, randomized trial performed in this patient population.
More than 41% of EB target wounds that were treated with Oleogel-S10 healed within 45 days, compared with about 29% of target wounds treated with placebo, in the EASE phase 3 trial, conducted at 58 sites in 28 countries.
A group of rare genetic disorders, EB “is described as the worst disease you’ve never heard of,” explained lead investigator Dedee Murrell, MD, director of dermatology, St. George Hospital at the University of New South Wales, Sydney. “It starts in children and is like having burns that heal with scars, and no treatment has been approved for it” by the Food and Drug Administration.
“This is the first large clinical trial with placebo of a topical treatment that’s worked for this terrible disease,” Dr. Murrell said in an interview. She noted that standard EB treatment currently consists of applying nonstick dressings to wounds to protect skin from trauma and infection.
Dr. Murrell, who has focused her work on EB patients since 1990, presented the findings at the virtual annual Congress of the European Academy of Dermatology and Venereology.
The trial enrolled 223 patients (average age, 12 years, but ages ranged to 81 years) with three types of EB, including dystrophic and junctional EB and Kindler syndrome. For each participant, a target wound was selected for use as the primary efficacy endpoint. Those wounds had a partial thickness of between 10 cm2 and 50 cm2 and lasted between 21 days and 9 months. Patients were stratified into groups depending on type of EB and size of target wound.
Participants were randomly assigned to receive either Oleogel-S10 (n = 109) or placebo (n = 114). All applied the blinded-study gel to all their wounds at least every 4 days at the time dressings were changed.
The primary endpoint was the percentage of patients whose target wounds completely closed within 45 days. Key secondary endpoints included time to wound healing and percentage of target wounds that healed within 90 days of treatment; incidence and severity of target wound infection; change in total body wound burden, as measured by the Epidermolysis Bullosa Disease Activity and Scarring Index skin activity subscore; change in itching, as measured by the Itch Man Scale and the Leuven Itch Scale; and adverse events.
Nearly 92% of patients who were treated with Oleogel-S10 completed the double-blind phase of the trial, compared with nearly 87% who received placebo. As noted, the primary endpoint was met, with 41.3% of Oleogel-S10 patients achieving target wound closure within 45 days, compared with 28.9% of the patients who received placebo (P = .013).
But the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of Oleogel-S10 patients achieving wound closure vs. 43.9% of control patients.
Target-wound infection occurred in eight participants, including three who used Oleogel-S10 and five who received placebo; all moderate or severe infections occurred in patients who received placebo. Total wound burden was reduced to a greater extent among Oleogel-S10 patients by day 60, but there was no apparent difference at day 90.
Both treatment groups reported qualitative improvements in itch, with no significant differences between groups. The prevalence of adverse events was also similar between groups (Oleogel-S10, 81.7%; placebo, 80.7%). The most frequently reported adverse events among Oleogel-S10 patients, compared with patients who received placebo, were wound complications, pyrexia, wound infection, pruritus, and anemia; only 4.5% of adverse events were deemed severe.
Dr. Murrell said that, on the basis of the trial results, she expects the FDA to fast-track approval of Oleogel-S10, which contains triterpene extract and sunflower oil.
The gel is “a treatment patients will be able to put under their dressings, added to normal treatment, which will accelerate their wound healing, with no significant increase in any side effects,” she added.
Jemima Mellerio, MD, of St. Thomas’ Hospital in London who sees about 400 EB patients each year, agreed with Dr. Murrell that the results are “very exciting.” Dr. Mellerio was not involved in the study.
“Practicing dermatologists seeing people with EB will have something to offer that appears to speed up wound healing in chronic wounds,” Dr. Mellerio said in an interview. “It’s a positive option rather than just supportive treatment, something that makes a difference to the natural history of wounds.”
She said the trial’s biggest strength was including “such a large cohort of patients.
“It’s extremely difficult to do that kind of study, especially with a placebo-controlled arm and especially in a rare disease,” Dr. Mellerio said. “If you think about the product itself, it’s easy to apply, so it’s not particularly onerous for people to add to their daily regimen of dressings.”
The study was funded by Amryt Pharma. Dr. Murrell is an advisory board member for Amryt Pharma. Dr. Mellerio is a consultant for Amryt Pharma.
A version of this article originally appeared on Medscape.com.
Mirikizumab beats placebo, secukinumab for psoriasis
The investigational monoclonal antibody according to new long-term OASIS-2 trial data.
Both doses of mirikizumab in the international, double-blind trial achieved improvements in Psoriasis Area and Severity Index (PASI) scores in larger numbers of participants at week 52 than secukinumab (Cosentyx), with low adverse event rates.
If approved, mirikizumab, which binds the p19 subunit of IL-23, would join three other IL-23 drugs already marketed in the United States for moderate to severe psoriasis, said OASIS-2 lead investigator Kim A. Papp, MD, PhD, founder and president of Probity Medical Research in Waterloo, Ont.
But Dr. Papp feels larger studies “will be necessary to put these data into perspective,” he said during a presentation at the virtual annual European Academy of Dermatology and Venereology Congress.
“Probably the most important takeaway here is that we may have another option to choose from,” Dr. Papp said in an interview. “People tend to think we have an adequate stable of treatment options, and I would argue we do not.”
“There are variations over time that occur in terms of an individual’s biological response, and the consequence is that nothing we have works for everyone, and nothing we have works forever,” he added. Psoriasis biologics “are increasingly competent, compared to medications we had even 5 or 10 years ago ... but they still don’t satisfy all our needs, so we do need to keep replenishing our stock.”
The multicenter trial included 1,465 patients who were randomly split into four groups. Subcutaneously, one group received 250 mg of mirikizumab every 4 weeks, and then 250 mg of the drug every 8 weeks starting at week 16. Another group received 250 mg of mirikizumab every 4 weeks and then 125 mg every 8 weeks starting at week 16.
The third group received 300 mg of secukinumab weekly for 4 weeks and then every 4 weeks starting at week 4. The last group received placebo every 4 weeks, and then 250 mg of mirikizumab every 4 weeks from week 16 to 32 and every 8 weeks thereafter.
Primary endpoints measured the percentage of patients achieving a static Physician’s Global Assessment (sPGA) of 0 or 1, with an improvement of at least 2 points from baseline; and the proportion of patients with PASI 90 at week 16, compared with placebo.
Major secondary endpoints were PASI 75 and PASI 100, compared with placebo at week 16; an sPGA of 0 or 1 and PASI 90 noninferiority, compared with secukinumab at week 16; and sPGA of 0 or 1, PASI 90, and PASI 100 superiority, compared with secukinumab at week 52.
More than 91% of participants completed all 52 weeks in the trial. Mirikizumab met primary endpoints compared with placebo and major secondary endpoints vs secukinumab at week 16 (P < .001). PASI 90 and sPGA (0,1) response rates far exceeded placebo for both 250 mg mirikizumab (74.4% and 79.7%, respectively) and secukinumab (72.8% and 76.3%, respectively).
At week 52, major secondary endpoints for both mirikizumab doses were superior to secukinumab (all P < .001). PASI 90 was achieved by 81.4% of 125 mg and 82.4% of 250 mg mirikizumab patients versus 69.4% of secukinumab patients; sPGA (0,1) by 83.1% of 125 mg and 83.3% of 250 mg mirikizumab patients versus 68.5% of secukinumab patients; and PASI 100 by 53.9% of 125 mg and 58.8% of 250 mg mirikizumab patients versus 42.9% of secukinumab patients.
Treatment-associated adverse effects were similar across all treatment groups and study periods. The most common were nasopharyngitis, upper respiratory tract infection, headache, back pain, and arthralgia. But serious adverse effects were minimal, Dr. Papp said. One death occurred in a mirikizumab patient from acute MI, which was deemed unrelated to the study drug.
Myrto Georgia Trakatelli, MD, PhD, from Aristotle University of Thessaloniki (Greece), said the results indicate that dermatologists “should not be afraid to use” mirikizumab long term if it is approved by the Food and Drug Administration.
“Sometimes patients use many treatments for a long time and all of a sudden, they stop working,” Dr. Trakatelli said in an interview. “A new biologic is always welcome because we do see patients not responding to other treatment.”
But Dr. Trakatelli said “a point that troubled me in the study” was that mirikizumab was compared with an IL-17 inhibitor “instead of a molecule targeting IL-23, such as guselkumab [Tremfya], for example.”
“I would have liked to see a head-to-head comparison with a molecule that blocks the same target,” said Dr. Trakatelli, chair of the EADV education committee.
Dr. Papp countered that “there are various reasons for running comparator studies.” Secukinumab, he said, “was the market leader and was widely used, so it makes sense that one is going to compare against a product as the market lead.”
“Not to say there won’t be future studies” in which mirikizumab is compared “head to head with IL-23s,” Dr. Papp added.
But larger patient numbers and longer treatment times are still needed with mirikizumab “to characterize the level of response, duration of response, and any adverse event profiles,” Dr. Papp stressed.
“One study does not a drug make,” he said. “It’s just exciting that we still have things to offer. This is an important example, and of course opportunity, for patients.”
The trial was funded by Lilly. Dr. Papp disclosed financial relationships with AbbVie, Amgen, Astellas, Valeant, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB. Dr. Trakatelli is a speaker for Novartis.
A version of this article originally appeared on Medscape.com.
The investigational monoclonal antibody according to new long-term OASIS-2 trial data.
Both doses of mirikizumab in the international, double-blind trial achieved improvements in Psoriasis Area and Severity Index (PASI) scores in larger numbers of participants at week 52 than secukinumab (Cosentyx), with low adverse event rates.
If approved, mirikizumab, which binds the p19 subunit of IL-23, would join three other IL-23 drugs already marketed in the United States for moderate to severe psoriasis, said OASIS-2 lead investigator Kim A. Papp, MD, PhD, founder and president of Probity Medical Research in Waterloo, Ont.
But Dr. Papp feels larger studies “will be necessary to put these data into perspective,” he said during a presentation at the virtual annual European Academy of Dermatology and Venereology Congress.
“Probably the most important takeaway here is that we may have another option to choose from,” Dr. Papp said in an interview. “People tend to think we have an adequate stable of treatment options, and I would argue we do not.”
“There are variations over time that occur in terms of an individual’s biological response, and the consequence is that nothing we have works for everyone, and nothing we have works forever,” he added. Psoriasis biologics “are increasingly competent, compared to medications we had even 5 or 10 years ago ... but they still don’t satisfy all our needs, so we do need to keep replenishing our stock.”
The multicenter trial included 1,465 patients who were randomly split into four groups. Subcutaneously, one group received 250 mg of mirikizumab every 4 weeks, and then 250 mg of the drug every 8 weeks starting at week 16. Another group received 250 mg of mirikizumab every 4 weeks and then 125 mg every 8 weeks starting at week 16.
The third group received 300 mg of secukinumab weekly for 4 weeks and then every 4 weeks starting at week 4. The last group received placebo every 4 weeks, and then 250 mg of mirikizumab every 4 weeks from week 16 to 32 and every 8 weeks thereafter.
Primary endpoints measured the percentage of patients achieving a static Physician’s Global Assessment (sPGA) of 0 or 1, with an improvement of at least 2 points from baseline; and the proportion of patients with PASI 90 at week 16, compared with placebo.
Major secondary endpoints were PASI 75 and PASI 100, compared with placebo at week 16; an sPGA of 0 or 1 and PASI 90 noninferiority, compared with secukinumab at week 16; and sPGA of 0 or 1, PASI 90, and PASI 100 superiority, compared with secukinumab at week 52.
More than 91% of participants completed all 52 weeks in the trial. Mirikizumab met primary endpoints compared with placebo and major secondary endpoints vs secukinumab at week 16 (P < .001). PASI 90 and sPGA (0,1) response rates far exceeded placebo for both 250 mg mirikizumab (74.4% and 79.7%, respectively) and secukinumab (72.8% and 76.3%, respectively).
At week 52, major secondary endpoints for both mirikizumab doses were superior to secukinumab (all P < .001). PASI 90 was achieved by 81.4% of 125 mg and 82.4% of 250 mg mirikizumab patients versus 69.4% of secukinumab patients; sPGA (0,1) by 83.1% of 125 mg and 83.3% of 250 mg mirikizumab patients versus 68.5% of secukinumab patients; and PASI 100 by 53.9% of 125 mg and 58.8% of 250 mg mirikizumab patients versus 42.9% of secukinumab patients.
Treatment-associated adverse effects were similar across all treatment groups and study periods. The most common were nasopharyngitis, upper respiratory tract infection, headache, back pain, and arthralgia. But serious adverse effects were minimal, Dr. Papp said. One death occurred in a mirikizumab patient from acute MI, which was deemed unrelated to the study drug.
Myrto Georgia Trakatelli, MD, PhD, from Aristotle University of Thessaloniki (Greece), said the results indicate that dermatologists “should not be afraid to use” mirikizumab long term if it is approved by the Food and Drug Administration.
“Sometimes patients use many treatments for a long time and all of a sudden, they stop working,” Dr. Trakatelli said in an interview. “A new biologic is always welcome because we do see patients not responding to other treatment.”
But Dr. Trakatelli said “a point that troubled me in the study” was that mirikizumab was compared with an IL-17 inhibitor “instead of a molecule targeting IL-23, such as guselkumab [Tremfya], for example.”
“I would have liked to see a head-to-head comparison with a molecule that blocks the same target,” said Dr. Trakatelli, chair of the EADV education committee.
Dr. Papp countered that “there are various reasons for running comparator studies.” Secukinumab, he said, “was the market leader and was widely used, so it makes sense that one is going to compare against a product as the market lead.”
“Not to say there won’t be future studies” in which mirikizumab is compared “head to head with IL-23s,” Dr. Papp added.
But larger patient numbers and longer treatment times are still needed with mirikizumab “to characterize the level of response, duration of response, and any adverse event profiles,” Dr. Papp stressed.
“One study does not a drug make,” he said. “It’s just exciting that we still have things to offer. This is an important example, and of course opportunity, for patients.”
The trial was funded by Lilly. Dr. Papp disclosed financial relationships with AbbVie, Amgen, Astellas, Valeant, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB. Dr. Trakatelli is a speaker for Novartis.
A version of this article originally appeared on Medscape.com.
The investigational monoclonal antibody according to new long-term OASIS-2 trial data.
Both doses of mirikizumab in the international, double-blind trial achieved improvements in Psoriasis Area and Severity Index (PASI) scores in larger numbers of participants at week 52 than secukinumab (Cosentyx), with low adverse event rates.
If approved, mirikizumab, which binds the p19 subunit of IL-23, would join three other IL-23 drugs already marketed in the United States for moderate to severe psoriasis, said OASIS-2 lead investigator Kim A. Papp, MD, PhD, founder and president of Probity Medical Research in Waterloo, Ont.
But Dr. Papp feels larger studies “will be necessary to put these data into perspective,” he said during a presentation at the virtual annual European Academy of Dermatology and Venereology Congress.
“Probably the most important takeaway here is that we may have another option to choose from,” Dr. Papp said in an interview. “People tend to think we have an adequate stable of treatment options, and I would argue we do not.”
“There are variations over time that occur in terms of an individual’s biological response, and the consequence is that nothing we have works for everyone, and nothing we have works forever,” he added. Psoriasis biologics “are increasingly competent, compared to medications we had even 5 or 10 years ago ... but they still don’t satisfy all our needs, so we do need to keep replenishing our stock.”
The multicenter trial included 1,465 patients who were randomly split into four groups. Subcutaneously, one group received 250 mg of mirikizumab every 4 weeks, and then 250 mg of the drug every 8 weeks starting at week 16. Another group received 250 mg of mirikizumab every 4 weeks and then 125 mg every 8 weeks starting at week 16.
The third group received 300 mg of secukinumab weekly for 4 weeks and then every 4 weeks starting at week 4. The last group received placebo every 4 weeks, and then 250 mg of mirikizumab every 4 weeks from week 16 to 32 and every 8 weeks thereafter.
Primary endpoints measured the percentage of patients achieving a static Physician’s Global Assessment (sPGA) of 0 or 1, with an improvement of at least 2 points from baseline; and the proportion of patients with PASI 90 at week 16, compared with placebo.
Major secondary endpoints were PASI 75 and PASI 100, compared with placebo at week 16; an sPGA of 0 or 1 and PASI 90 noninferiority, compared with secukinumab at week 16; and sPGA of 0 or 1, PASI 90, and PASI 100 superiority, compared with secukinumab at week 52.
More than 91% of participants completed all 52 weeks in the trial. Mirikizumab met primary endpoints compared with placebo and major secondary endpoints vs secukinumab at week 16 (P < .001). PASI 90 and sPGA (0,1) response rates far exceeded placebo for both 250 mg mirikizumab (74.4% and 79.7%, respectively) and secukinumab (72.8% and 76.3%, respectively).
At week 52, major secondary endpoints for both mirikizumab doses were superior to secukinumab (all P < .001). PASI 90 was achieved by 81.4% of 125 mg and 82.4% of 250 mg mirikizumab patients versus 69.4% of secukinumab patients; sPGA (0,1) by 83.1% of 125 mg and 83.3% of 250 mg mirikizumab patients versus 68.5% of secukinumab patients; and PASI 100 by 53.9% of 125 mg and 58.8% of 250 mg mirikizumab patients versus 42.9% of secukinumab patients.
Treatment-associated adverse effects were similar across all treatment groups and study periods. The most common were nasopharyngitis, upper respiratory tract infection, headache, back pain, and arthralgia. But serious adverse effects were minimal, Dr. Papp said. One death occurred in a mirikizumab patient from acute MI, which was deemed unrelated to the study drug.
Myrto Georgia Trakatelli, MD, PhD, from Aristotle University of Thessaloniki (Greece), said the results indicate that dermatologists “should not be afraid to use” mirikizumab long term if it is approved by the Food and Drug Administration.
“Sometimes patients use many treatments for a long time and all of a sudden, they stop working,” Dr. Trakatelli said in an interview. “A new biologic is always welcome because we do see patients not responding to other treatment.”
But Dr. Trakatelli said “a point that troubled me in the study” was that mirikizumab was compared with an IL-17 inhibitor “instead of a molecule targeting IL-23, such as guselkumab [Tremfya], for example.”
“I would have liked to see a head-to-head comparison with a molecule that blocks the same target,” said Dr. Trakatelli, chair of the EADV education committee.
Dr. Papp countered that “there are various reasons for running comparator studies.” Secukinumab, he said, “was the market leader and was widely used, so it makes sense that one is going to compare against a product as the market lead.”
“Not to say there won’t be future studies” in which mirikizumab is compared “head to head with IL-23s,” Dr. Papp added.
But larger patient numbers and longer treatment times are still needed with mirikizumab “to characterize the level of response, duration of response, and any adverse event profiles,” Dr. Papp stressed.
“One study does not a drug make,” he said. “It’s just exciting that we still have things to offer. This is an important example, and of course opportunity, for patients.”
The trial was funded by Lilly. Dr. Papp disclosed financial relationships with AbbVie, Amgen, Astellas, Valeant, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB. Dr. Trakatelli is a speaker for Novartis.
A version of this article originally appeared on Medscape.com.
FROM THE EADV CONGRESS
Hand eczema: Pan-JAK inhibitor delgocitinib shows dose-dependent response in phase 2b trial
a new international phase 2b research suggests.
An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.
“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.
“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”
Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.
Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.
“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”
The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”
Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.
The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.
At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).
This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).
“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”
Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.
Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.
It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.
“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”
The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
a new international phase 2b research suggests.
An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.
“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.
“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”
Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.
Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.
“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”
The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”
Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.
The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.
At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).
This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).
“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”
Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.
Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.
It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.
“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”
The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
a new international phase 2b research suggests.
An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.
“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.
“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”
Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.
Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.
“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”
The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”
Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.
The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.
At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).
This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).
“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”
Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.
Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.
It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.
“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”
The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM THE EADV CONGRESS
Med student’s cardiac crisis a COVID-era medical mystery
Within minutes of her arrival at Community North Hospital in Indianapolis, Ramya Yeleti’s vital signs plummeted; her pulse was at 45 beats per minute and her ejection fraction was hovering near 10%. “I definitely thought there was a chance I would close my eyes and never open them again, but I only had a few seconds to process that,” she recalled. Then everything went black. Ramya fell unconscious as shock pads were positioned and a swarm of clinicians prepared to insert an Impella heart pump through a catheter into her aorta.
The third-year medical student and aspiring psychiatrist had been doing in-person neurology rotations in July when she began to experience fever and uncontrolled vomiting. Her initial thought was that she must have caught the flu from a patient.
After all, Ramya, along with her father Ram Yeleti, MD, mother Indira, and twin sister Divya, had all weathered COVID-19 in previous months and later tested positive for SARS-CoV-2 antibodies. The only family member who had been spared was her younger brother Rohith.
Indira suffered a severe case, requiring ICU care for 2 days but no ventilator; the others experienced mostly mild symptoms. Ramya — who was studying for her third-year board exams after classes at Marian University College of Osteopathic Medicine in Indianapolis went virtual in March — was left with lingering fatigue; however, her cough and muscle aches abated and her sense of taste and smell returned. When she started rotations, she thought her life was getting back to normal.
Ramya’s flu symptoms did not improve. A university-mandated rapid COVID test came back negative, but 2 more days of vomiting started to worry both her and her father, who is a cardiologist and chief physician executive at Community Health Network in Indianapolis. After Ramya felt some chest pain, she asked her father to listen to her heart. All sounded normal, and Ram prescribed ondansetron for her nausea.
But the antiemetic didn’t work, and by the next morning both father and daughter were convinced that they needed to head to the emergency department.
“I wanted to double-check if I was missing something about her being dehydrated,” Ram told Medscape Medical News. “Several things can cause protracted nausea, like hepatitis, appendicitis, or another infection. I feel terribly guilty I didn’t realize she had a heart condition.”
A surprising turn for the worst
Ramya’s subtle symptoms quickly gave way to the dramatic cardiac crisis that unfolded just after her arrival at Community North. “Her EKG looked absolutely horrendous, like a 75-year-old having a heart attack,” Ram said.
As a cardiologist, he knew his daughter’s situation was growing dire when he heard physicians shouting that the Impella wasn’t working and she needed extracorporeal membrane oxygenation (ECMO).
“At that point, I didn’t think she’d survive,” her father recalled. “We had 10 physicians in the room who worked on her for 5 hours to get her stabilized.”
“It was especially traumatic because, obviously, I knew exactly what was happening,” he added. “You can’t sugarcoat anything.”
After being connected to the heart–lung equipment, Ramya was transferred to IU Health Methodist Hospital, also in Indianapolis, where she was tested again for COVID-19. Unlike the rapid test administered just days earlier, the PCR assay came back positive.
“I knew she had acute myocarditis, but coronavirus never crossed my mind,” said Ram.
“As we were dealing with her heart, we were also dealing with this challenge: she was coming back positive for COVID-19 again,” said Roopa Rao, MD, the heart failure transplant cardiologist at IU Health who treated Ramya.
“We weren’t sure whether we were dealing with an active infection or dead virus” from her previous infection, Rao said, “so we started treating her like she had active COVID-19 and gave her remdesivir, convalescent plasma, and steroids, which was the protocol in our hospital.”
A biopsy of Ramya’s heart tissue, along with blood tests, indicated a past parvovirus infection. It’s possible that Ramya’s previous coronavirus infection made her susceptible to heart damage from a newer parvovirus infection, said Rao. Either virus, or both together, could have been responsible for the calamity.
Although it was unheard of during Ramya’s cardiac crisis in early August, evolving evidence now raises the possibility that she is one of a handful of people in the world to be reinfected with SARS-CoV-2. Also emerging are cases of COVID-related myocarditis and other extreme heart complications, particularly in young people.
“At the time, it wasn’t really clear if people could have another infection so quickly,” Rao told Medscape Medical News. “It is possible she is one of these rare individuals to have COVID-19 twice. I’m hoping at some point we will have some clarity.”
“I would favor a coinfection as probably the triggering factor for her sickness,” she said. “It may take some time, but like any other disease — and it doesn’t look like COVID will go away magically — I hope we’ll have some answers down the road.”
Another wrinkle
The next 48 hours brought astonishing news: Ramya’s heart function had rebounded to nearly normal, and her ejection fraction increased to about 45%. Heart transplantation wouldn’t be necessary, although Rao stood poised to follow through if ECMO only sustained, rather than improved, Ramya’s prognosis.
“Ramya was so sick that if she didn’t recover, the only option would be a heart transplant,” said Rao. “But we wanted to do everything to keep that heart.”
After steroid and COVID treatment, Ramya’s heart started to come back. “It didn’t make sense to me,” said Rao. “I don’t know what helped. If we hadn’t done ECMO, her heart probably wouldn’t have recovered, so I would say we have to support these patients and give them time for the heart to recover, even to the point of ECMO.”
Despite the good news, Ramya’s survival still hung in the balance. When she was disconnected from ECMO, clinicians discovered that the Impella device had caused a rare complication, damaging her mitral valve. The valve could be repaired surgically, but both Rao and Ram felt great trepidation at the prospect of cardiopulmonary bypass during the open-heart procedure.
“They would need to stop her heart and restart it, and I was concerned it would not restart,” Ram explained. “I didn’t like the idea of open-heart surgery, but my biggest fear was she was not going to survive it because of a really fresh, sick heart.”
The cardiologists’ fears did, in fact, come to pass: it took an hour to coax Ramya’s heart back at the end of surgery. But, just as the surgeon was preparing to reconnect Ramya to ECMO in desperation, “her heart recovered again,” Rao reported.
“Some things you never forget in life,” she said. “I can’t describe how everyone in the OR felt, all taking care of her. I told Ramya, ‘you are a fighter’.”
New strength
Six days would pass before Ramya woke up and learned of the astounding series of events that saved her. She knew “something was really wrong” because of the incision at the center of her chest, but learning she’d been on ECMO and the heart transplant list drove home how close to death she’d actually come.
“Most people don’t get off ECMO; they die on it,” she said. “And the chances of dying on the heart transplant list are very high. It was very strange to me that this was my story all of a sudden, when a week and a half earlier I was on rotation.”
Ongoing physical therapy over the past 3 months has transformed Ramya from a state of profound physical weakness to a place of relative strength. The now-fourth-year med student is turning 26 in November and is hungry to restart in-person rotations. Her downtime has been filled in part with researching myocarditis and collaborating with Rao on her own case study for journal publication.
But the mental trauma from her experience has girded her in ways she knows will make her stronger personally and professionally in the years ahead.
“It’s still very hard. I’m still recovering,” she acknowledged. “I described it to my therapist as an invisible wound on my brain.”
“When I came out of the hospital, I still had ECMO wounds, deep gashes on my legs that affected how fast and how long I could walk,” she said. “I felt like the same thing was going on my brain — a huge cut no one could see.”
Her intention to specialize in psychiatry has become more pressing now that Ramya has realized the impact of trauma on mental health.
“My body failing me was awful, but I could handle it,” she said. “Losing any part of my mind would have been way worse. I want to take care of that in my patients.”
This article first appeared on Medscape.com.
Within minutes of her arrival at Community North Hospital in Indianapolis, Ramya Yeleti’s vital signs plummeted; her pulse was at 45 beats per minute and her ejection fraction was hovering near 10%. “I definitely thought there was a chance I would close my eyes and never open them again, but I only had a few seconds to process that,” she recalled. Then everything went black. Ramya fell unconscious as shock pads were positioned and a swarm of clinicians prepared to insert an Impella heart pump through a catheter into her aorta.
The third-year medical student and aspiring psychiatrist had been doing in-person neurology rotations in July when she began to experience fever and uncontrolled vomiting. Her initial thought was that she must have caught the flu from a patient.
After all, Ramya, along with her father Ram Yeleti, MD, mother Indira, and twin sister Divya, had all weathered COVID-19 in previous months and later tested positive for SARS-CoV-2 antibodies. The only family member who had been spared was her younger brother Rohith.
Indira suffered a severe case, requiring ICU care for 2 days but no ventilator; the others experienced mostly mild symptoms. Ramya — who was studying for her third-year board exams after classes at Marian University College of Osteopathic Medicine in Indianapolis went virtual in March — was left with lingering fatigue; however, her cough and muscle aches abated and her sense of taste and smell returned. When she started rotations, she thought her life was getting back to normal.
Ramya’s flu symptoms did not improve. A university-mandated rapid COVID test came back negative, but 2 more days of vomiting started to worry both her and her father, who is a cardiologist and chief physician executive at Community Health Network in Indianapolis. After Ramya felt some chest pain, she asked her father to listen to her heart. All sounded normal, and Ram prescribed ondansetron for her nausea.
But the antiemetic didn’t work, and by the next morning both father and daughter were convinced that they needed to head to the emergency department.
“I wanted to double-check if I was missing something about her being dehydrated,” Ram told Medscape Medical News. “Several things can cause protracted nausea, like hepatitis, appendicitis, or another infection. I feel terribly guilty I didn’t realize she had a heart condition.”
A surprising turn for the worst
Ramya’s subtle symptoms quickly gave way to the dramatic cardiac crisis that unfolded just after her arrival at Community North. “Her EKG looked absolutely horrendous, like a 75-year-old having a heart attack,” Ram said.
As a cardiologist, he knew his daughter’s situation was growing dire when he heard physicians shouting that the Impella wasn’t working and she needed extracorporeal membrane oxygenation (ECMO).
“At that point, I didn’t think she’d survive,” her father recalled. “We had 10 physicians in the room who worked on her for 5 hours to get her stabilized.”
“It was especially traumatic because, obviously, I knew exactly what was happening,” he added. “You can’t sugarcoat anything.”
After being connected to the heart–lung equipment, Ramya was transferred to IU Health Methodist Hospital, also in Indianapolis, where she was tested again for COVID-19. Unlike the rapid test administered just days earlier, the PCR assay came back positive.
“I knew she had acute myocarditis, but coronavirus never crossed my mind,” said Ram.
“As we were dealing with her heart, we were also dealing with this challenge: she was coming back positive for COVID-19 again,” said Roopa Rao, MD, the heart failure transplant cardiologist at IU Health who treated Ramya.
“We weren’t sure whether we were dealing with an active infection or dead virus” from her previous infection, Rao said, “so we started treating her like she had active COVID-19 and gave her remdesivir, convalescent plasma, and steroids, which was the protocol in our hospital.”
A biopsy of Ramya’s heart tissue, along with blood tests, indicated a past parvovirus infection. It’s possible that Ramya’s previous coronavirus infection made her susceptible to heart damage from a newer parvovirus infection, said Rao. Either virus, or both together, could have been responsible for the calamity.
Although it was unheard of during Ramya’s cardiac crisis in early August, evolving evidence now raises the possibility that she is one of a handful of people in the world to be reinfected with SARS-CoV-2. Also emerging are cases of COVID-related myocarditis and other extreme heart complications, particularly in young people.
“At the time, it wasn’t really clear if people could have another infection so quickly,” Rao told Medscape Medical News. “It is possible she is one of these rare individuals to have COVID-19 twice. I’m hoping at some point we will have some clarity.”
“I would favor a coinfection as probably the triggering factor for her sickness,” she said. “It may take some time, but like any other disease — and it doesn’t look like COVID will go away magically — I hope we’ll have some answers down the road.”
Another wrinkle
The next 48 hours brought astonishing news: Ramya’s heart function had rebounded to nearly normal, and her ejection fraction increased to about 45%. Heart transplantation wouldn’t be necessary, although Rao stood poised to follow through if ECMO only sustained, rather than improved, Ramya’s prognosis.
“Ramya was so sick that if she didn’t recover, the only option would be a heart transplant,” said Rao. “But we wanted to do everything to keep that heart.”
After steroid and COVID treatment, Ramya’s heart started to come back. “It didn’t make sense to me,” said Rao. “I don’t know what helped. If we hadn’t done ECMO, her heart probably wouldn’t have recovered, so I would say we have to support these patients and give them time for the heart to recover, even to the point of ECMO.”
Despite the good news, Ramya’s survival still hung in the balance. When she was disconnected from ECMO, clinicians discovered that the Impella device had caused a rare complication, damaging her mitral valve. The valve could be repaired surgically, but both Rao and Ram felt great trepidation at the prospect of cardiopulmonary bypass during the open-heart procedure.
“They would need to stop her heart and restart it, and I was concerned it would not restart,” Ram explained. “I didn’t like the idea of open-heart surgery, but my biggest fear was she was not going to survive it because of a really fresh, sick heart.”
The cardiologists’ fears did, in fact, come to pass: it took an hour to coax Ramya’s heart back at the end of surgery. But, just as the surgeon was preparing to reconnect Ramya to ECMO in desperation, “her heart recovered again,” Rao reported.
“Some things you never forget in life,” she said. “I can’t describe how everyone in the OR felt, all taking care of her. I told Ramya, ‘you are a fighter’.”
New strength
Six days would pass before Ramya woke up and learned of the astounding series of events that saved her. She knew “something was really wrong” because of the incision at the center of her chest, but learning she’d been on ECMO and the heart transplant list drove home how close to death she’d actually come.
“Most people don’t get off ECMO; they die on it,” she said. “And the chances of dying on the heart transplant list are very high. It was very strange to me that this was my story all of a sudden, when a week and a half earlier I was on rotation.”
Ongoing physical therapy over the past 3 months has transformed Ramya from a state of profound physical weakness to a place of relative strength. The now-fourth-year med student is turning 26 in November and is hungry to restart in-person rotations. Her downtime has been filled in part with researching myocarditis and collaborating with Rao on her own case study for journal publication.
But the mental trauma from her experience has girded her in ways she knows will make her stronger personally and professionally in the years ahead.
“It’s still very hard. I’m still recovering,” she acknowledged. “I described it to my therapist as an invisible wound on my brain.”
“When I came out of the hospital, I still had ECMO wounds, deep gashes on my legs that affected how fast and how long I could walk,” she said. “I felt like the same thing was going on my brain — a huge cut no one could see.”
Her intention to specialize in psychiatry has become more pressing now that Ramya has realized the impact of trauma on mental health.
“My body failing me was awful, but I could handle it,” she said. “Losing any part of my mind would have been way worse. I want to take care of that in my patients.”
This article first appeared on Medscape.com.
Within minutes of her arrival at Community North Hospital in Indianapolis, Ramya Yeleti’s vital signs plummeted; her pulse was at 45 beats per minute and her ejection fraction was hovering near 10%. “I definitely thought there was a chance I would close my eyes and never open them again, but I only had a few seconds to process that,” she recalled. Then everything went black. Ramya fell unconscious as shock pads were positioned and a swarm of clinicians prepared to insert an Impella heart pump through a catheter into her aorta.
The third-year medical student and aspiring psychiatrist had been doing in-person neurology rotations in July when she began to experience fever and uncontrolled vomiting. Her initial thought was that she must have caught the flu from a patient.
After all, Ramya, along with her father Ram Yeleti, MD, mother Indira, and twin sister Divya, had all weathered COVID-19 in previous months and later tested positive for SARS-CoV-2 antibodies. The only family member who had been spared was her younger brother Rohith.
Indira suffered a severe case, requiring ICU care for 2 days but no ventilator; the others experienced mostly mild symptoms. Ramya — who was studying for her third-year board exams after classes at Marian University College of Osteopathic Medicine in Indianapolis went virtual in March — was left with lingering fatigue; however, her cough and muscle aches abated and her sense of taste and smell returned. When she started rotations, she thought her life was getting back to normal.
Ramya’s flu symptoms did not improve. A university-mandated rapid COVID test came back negative, but 2 more days of vomiting started to worry both her and her father, who is a cardiologist and chief physician executive at Community Health Network in Indianapolis. After Ramya felt some chest pain, she asked her father to listen to her heart. All sounded normal, and Ram prescribed ondansetron for her nausea.
But the antiemetic didn’t work, and by the next morning both father and daughter were convinced that they needed to head to the emergency department.
“I wanted to double-check if I was missing something about her being dehydrated,” Ram told Medscape Medical News. “Several things can cause protracted nausea, like hepatitis, appendicitis, or another infection. I feel terribly guilty I didn’t realize she had a heart condition.”
A surprising turn for the worst
Ramya’s subtle symptoms quickly gave way to the dramatic cardiac crisis that unfolded just after her arrival at Community North. “Her EKG looked absolutely horrendous, like a 75-year-old having a heart attack,” Ram said.
As a cardiologist, he knew his daughter’s situation was growing dire when he heard physicians shouting that the Impella wasn’t working and she needed extracorporeal membrane oxygenation (ECMO).
“At that point, I didn’t think she’d survive,” her father recalled. “We had 10 physicians in the room who worked on her for 5 hours to get her stabilized.”
“It was especially traumatic because, obviously, I knew exactly what was happening,” he added. “You can’t sugarcoat anything.”
After being connected to the heart–lung equipment, Ramya was transferred to IU Health Methodist Hospital, also in Indianapolis, where she was tested again for COVID-19. Unlike the rapid test administered just days earlier, the PCR assay came back positive.
“I knew she had acute myocarditis, but coronavirus never crossed my mind,” said Ram.
“As we were dealing with her heart, we were also dealing with this challenge: she was coming back positive for COVID-19 again,” said Roopa Rao, MD, the heart failure transplant cardiologist at IU Health who treated Ramya.
“We weren’t sure whether we were dealing with an active infection or dead virus” from her previous infection, Rao said, “so we started treating her like she had active COVID-19 and gave her remdesivir, convalescent plasma, and steroids, which was the protocol in our hospital.”
A biopsy of Ramya’s heart tissue, along with blood tests, indicated a past parvovirus infection. It’s possible that Ramya’s previous coronavirus infection made her susceptible to heart damage from a newer parvovirus infection, said Rao. Either virus, or both together, could have been responsible for the calamity.
Although it was unheard of during Ramya’s cardiac crisis in early August, evolving evidence now raises the possibility that she is one of a handful of people in the world to be reinfected with SARS-CoV-2. Also emerging are cases of COVID-related myocarditis and other extreme heart complications, particularly in young people.
“At the time, it wasn’t really clear if people could have another infection so quickly,” Rao told Medscape Medical News. “It is possible she is one of these rare individuals to have COVID-19 twice. I’m hoping at some point we will have some clarity.”
“I would favor a coinfection as probably the triggering factor for her sickness,” she said. “It may take some time, but like any other disease — and it doesn’t look like COVID will go away magically — I hope we’ll have some answers down the road.”
Another wrinkle
The next 48 hours brought astonishing news: Ramya’s heart function had rebounded to nearly normal, and her ejection fraction increased to about 45%. Heart transplantation wouldn’t be necessary, although Rao stood poised to follow through if ECMO only sustained, rather than improved, Ramya’s prognosis.
“Ramya was so sick that if she didn’t recover, the only option would be a heart transplant,” said Rao. “But we wanted to do everything to keep that heart.”
After steroid and COVID treatment, Ramya’s heart started to come back. “It didn’t make sense to me,” said Rao. “I don’t know what helped. If we hadn’t done ECMO, her heart probably wouldn’t have recovered, so I would say we have to support these patients and give them time for the heart to recover, even to the point of ECMO.”
Despite the good news, Ramya’s survival still hung in the balance. When she was disconnected from ECMO, clinicians discovered that the Impella device had caused a rare complication, damaging her mitral valve. The valve could be repaired surgically, but both Rao and Ram felt great trepidation at the prospect of cardiopulmonary bypass during the open-heart procedure.
“They would need to stop her heart and restart it, and I was concerned it would not restart,” Ram explained. “I didn’t like the idea of open-heart surgery, but my biggest fear was she was not going to survive it because of a really fresh, sick heart.”
The cardiologists’ fears did, in fact, come to pass: it took an hour to coax Ramya’s heart back at the end of surgery. But, just as the surgeon was preparing to reconnect Ramya to ECMO in desperation, “her heart recovered again,” Rao reported.
“Some things you never forget in life,” she said. “I can’t describe how everyone in the OR felt, all taking care of her. I told Ramya, ‘you are a fighter’.”
New strength
Six days would pass before Ramya woke up and learned of the astounding series of events that saved her. She knew “something was really wrong” because of the incision at the center of her chest, but learning she’d been on ECMO and the heart transplant list drove home how close to death she’d actually come.
“Most people don’t get off ECMO; they die on it,” she said. “And the chances of dying on the heart transplant list are very high. It was very strange to me that this was my story all of a sudden, when a week and a half earlier I was on rotation.”
Ongoing physical therapy over the past 3 months has transformed Ramya from a state of profound physical weakness to a place of relative strength. The now-fourth-year med student is turning 26 in November and is hungry to restart in-person rotations. Her downtime has been filled in part with researching myocarditis and collaborating with Rao on her own case study for journal publication.
But the mental trauma from her experience has girded her in ways she knows will make her stronger personally and professionally in the years ahead.
“It’s still very hard. I’m still recovering,” she acknowledged. “I described it to my therapist as an invisible wound on my brain.”
“When I came out of the hospital, I still had ECMO wounds, deep gashes on my legs that affected how fast and how long I could walk,” she said. “I felt like the same thing was going on my brain — a huge cut no one could see.”
Her intention to specialize in psychiatry has become more pressing now that Ramya has realized the impact of trauma on mental health.
“My body failing me was awful, but I could handle it,” she said. “Losing any part of my mind would have been way worse. I want to take care of that in my patients.”
This article first appeared on Medscape.com.
Skin symptoms common in COVID-19 ‘long-haulers’
for more than 150 days, a new analysis revealed.
Evaluating data from an international registry of COVID-19 patients with dermatologic symptoms, researchers found that retiform purpura rashes are linked to severe COVID-19, with 100% of these patients requiring hospitalization and 82% experiencing acute respiratory distress syndrome (ARDS).
Meanwhile, pernio/chilblains rashes, dubbed “COVID toes,” are associated with milder disease and a 16% hospitalization rate. For all COVID-19–related skin symptoms, the average duration is 12 days.
“The skin is another organ system that we didn’t know could have long COVID” effects, said principal investigator Esther Freeman, MD, PhD, of the department of dermatology, Massachusetts General Hospital, Boston.
“The skin is really a window into how the body is working overall, so the fact that we could visually see persistent inflammation in long-hauler patients is particularly fascinating and gives us a chance to explore what’s going on,” Dr. Freeman said in an interview. “It certainly makes sense to me, knowing what we know about other organ systems, that there might be some long-lasting inflammation” in the skin as well.
The study is a result of the collaboration between the American Academy of Dermatology and the International League of Dermatological Societies, the international registry launched this past April. While the study included provider-supplied data from 990 cases spanning 39 countries, the registry now encompasses more than 1,000 patients from 41 countries, Dr. Freeman noted.
Dr. Freeman presented the data at the annual congress of the European Academy of Dermatology and Venereology.
Many studies have reported dermatologic effects of COVID-19 infection, but information was lacking about duration. The registry represents the largest dataset to date detailing these persistent skin symptoms and offers insight about how COVID-19 can affect many different organ systems even after patients recover from acute infection, Dr. Freeman said.
Eight different types of skin rashes were noted in the study group, of which 303 were lab-confirmed or suspected COVID-19 patients with skin symptoms. Of those, 224 total cases and 90 lab-confirmed cases included information on how long skin symptoms lasted. Lab tests for SARS-CoV-2 included polymerase chain reaction and serum antibody assays.
Dr. Freeman and associates defined “long-haulers” as patients with dermatologic symptoms of COVID-19 lasting 60 days or longer. These “outliers” are likely more prevalent than the registry suggests, she said, since not all providers initially reporting skin symptoms in patients updated that information over time.
“It’s important to understand that the registry is probably significantly underreporting the duration of symptoms and number of long-hauler patients,” she explained. “A registry is often a glimpse into a moment in time to these patients. To combat that, we followed up by email twice with providers to ask if patients’ symptoms were still ongoing or completed.”
Results showed a wide spectrum in average duration of symptoms among lab-confirmed COVID-19 patients, depending on specific rash. Urticaria lasted for a median of 4 days; morbilliform eruptions, 7 days; pernio/chilblains, 10 days; and papulosquamous eruptions, 20 days, with one long-hauler case lasting 70 days.
Five patients with pernio/chilblains were long-haulers, with toe symptoms enduring 60 days or longer. Only one went beyond 133 days with severe pernio and fatigue.
“The fact that we’re not necessarily seeing these long-hauler symptoms across every type of skin rash makes sense,” Dr. Freeman said. “Hives, for example, usually comes on acutely and leaves pretty rapidly. There are no reports of long-hauler hives.”
“That we’re really seeing these long-hauler symptoms in certain skin rashes really suggests that there’s a certain pathophysiology going in within that group of patients,” she added.
Dr. Freeman said not enough data have yet been generated to correlate long-standing COVID-19 skin symptoms with lasting cardiac, neurologic, or other symptoms of prolonged inflammation stemming from the virus.
Meanwhile, an EADV survey of 490 dermatologists revealed that just over one-third have seen patients presenting with skin signs of COVID-19. Moreover, 4% of dermatologists themselves tested positive for the virus.
Dr. Freeman encouraged all frontline clinicians assessing COVID-19 patients with skin symptoms to enter patients into the registry. But despite its strengths, the registry “can’t tell us what percentage of everyone who gets COVID will develop a skin finding or what percentage will be a long-hauler,” she said.
“A registry doesn’t have a denominator, so it’s like a giant case series,” she added.
“It will be very helpful going forward, as many places around the world experience second or third waves of COVID-19, to follow patients prospectively, acknowledge that patients will have symptoms lasting different amounts of time, and be aware these symptoms can occur on the skin,” she said.
Christopher Griffiths, MD, of the University of Manchester (England), praised the international registry as a valuable tool that will help clinicians better manage patients with COVID-19–related skin effects and predict prognosis.
“This has really brought the international dermatology community together, working on a focused goal relevant to all of us around the world,” Dr. Griffiths said in an interview. “It shows the power of communication and collaboration and what can be achieved in a short period of time.”
Dr. Freeman and Dr. Griffiths disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
for more than 150 days, a new analysis revealed.
Evaluating data from an international registry of COVID-19 patients with dermatologic symptoms, researchers found that retiform purpura rashes are linked to severe COVID-19, with 100% of these patients requiring hospitalization and 82% experiencing acute respiratory distress syndrome (ARDS).
Meanwhile, pernio/chilblains rashes, dubbed “COVID toes,” are associated with milder disease and a 16% hospitalization rate. For all COVID-19–related skin symptoms, the average duration is 12 days.
“The skin is another organ system that we didn’t know could have long COVID” effects, said principal investigator Esther Freeman, MD, PhD, of the department of dermatology, Massachusetts General Hospital, Boston.
“The skin is really a window into how the body is working overall, so the fact that we could visually see persistent inflammation in long-hauler patients is particularly fascinating and gives us a chance to explore what’s going on,” Dr. Freeman said in an interview. “It certainly makes sense to me, knowing what we know about other organ systems, that there might be some long-lasting inflammation” in the skin as well.
The study is a result of the collaboration between the American Academy of Dermatology and the International League of Dermatological Societies, the international registry launched this past April. While the study included provider-supplied data from 990 cases spanning 39 countries, the registry now encompasses more than 1,000 patients from 41 countries, Dr. Freeman noted.
Dr. Freeman presented the data at the annual congress of the European Academy of Dermatology and Venereology.
Many studies have reported dermatologic effects of COVID-19 infection, but information was lacking about duration. The registry represents the largest dataset to date detailing these persistent skin symptoms and offers insight about how COVID-19 can affect many different organ systems even after patients recover from acute infection, Dr. Freeman said.
Eight different types of skin rashes were noted in the study group, of which 303 were lab-confirmed or suspected COVID-19 patients with skin symptoms. Of those, 224 total cases and 90 lab-confirmed cases included information on how long skin symptoms lasted. Lab tests for SARS-CoV-2 included polymerase chain reaction and serum antibody assays.
Dr. Freeman and associates defined “long-haulers” as patients with dermatologic symptoms of COVID-19 lasting 60 days or longer. These “outliers” are likely more prevalent than the registry suggests, she said, since not all providers initially reporting skin symptoms in patients updated that information over time.
“It’s important to understand that the registry is probably significantly underreporting the duration of symptoms and number of long-hauler patients,” she explained. “A registry is often a glimpse into a moment in time to these patients. To combat that, we followed up by email twice with providers to ask if patients’ symptoms were still ongoing or completed.”
Results showed a wide spectrum in average duration of symptoms among lab-confirmed COVID-19 patients, depending on specific rash. Urticaria lasted for a median of 4 days; morbilliform eruptions, 7 days; pernio/chilblains, 10 days; and papulosquamous eruptions, 20 days, with one long-hauler case lasting 70 days.
Five patients with pernio/chilblains were long-haulers, with toe symptoms enduring 60 days or longer. Only one went beyond 133 days with severe pernio and fatigue.
“The fact that we’re not necessarily seeing these long-hauler symptoms across every type of skin rash makes sense,” Dr. Freeman said. “Hives, for example, usually comes on acutely and leaves pretty rapidly. There are no reports of long-hauler hives.”
“That we’re really seeing these long-hauler symptoms in certain skin rashes really suggests that there’s a certain pathophysiology going in within that group of patients,” she added.
Dr. Freeman said not enough data have yet been generated to correlate long-standing COVID-19 skin symptoms with lasting cardiac, neurologic, or other symptoms of prolonged inflammation stemming from the virus.
Meanwhile, an EADV survey of 490 dermatologists revealed that just over one-third have seen patients presenting with skin signs of COVID-19. Moreover, 4% of dermatologists themselves tested positive for the virus.
Dr. Freeman encouraged all frontline clinicians assessing COVID-19 patients with skin symptoms to enter patients into the registry. But despite its strengths, the registry “can’t tell us what percentage of everyone who gets COVID will develop a skin finding or what percentage will be a long-hauler,” she said.
“A registry doesn’t have a denominator, so it’s like a giant case series,” she added.
“It will be very helpful going forward, as many places around the world experience second or third waves of COVID-19, to follow patients prospectively, acknowledge that patients will have symptoms lasting different amounts of time, and be aware these symptoms can occur on the skin,” she said.
Christopher Griffiths, MD, of the University of Manchester (England), praised the international registry as a valuable tool that will help clinicians better manage patients with COVID-19–related skin effects and predict prognosis.
“This has really brought the international dermatology community together, working on a focused goal relevant to all of us around the world,” Dr. Griffiths said in an interview. “It shows the power of communication and collaboration and what can be achieved in a short period of time.”
Dr. Freeman and Dr. Griffiths disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
for more than 150 days, a new analysis revealed.
Evaluating data from an international registry of COVID-19 patients with dermatologic symptoms, researchers found that retiform purpura rashes are linked to severe COVID-19, with 100% of these patients requiring hospitalization and 82% experiencing acute respiratory distress syndrome (ARDS).
Meanwhile, pernio/chilblains rashes, dubbed “COVID toes,” are associated with milder disease and a 16% hospitalization rate. For all COVID-19–related skin symptoms, the average duration is 12 days.
“The skin is another organ system that we didn’t know could have long COVID” effects, said principal investigator Esther Freeman, MD, PhD, of the department of dermatology, Massachusetts General Hospital, Boston.
“The skin is really a window into how the body is working overall, so the fact that we could visually see persistent inflammation in long-hauler patients is particularly fascinating and gives us a chance to explore what’s going on,” Dr. Freeman said in an interview. “It certainly makes sense to me, knowing what we know about other organ systems, that there might be some long-lasting inflammation” in the skin as well.
The study is a result of the collaboration between the American Academy of Dermatology and the International League of Dermatological Societies, the international registry launched this past April. While the study included provider-supplied data from 990 cases spanning 39 countries, the registry now encompasses more than 1,000 patients from 41 countries, Dr. Freeman noted.
Dr. Freeman presented the data at the annual congress of the European Academy of Dermatology and Venereology.
Many studies have reported dermatologic effects of COVID-19 infection, but information was lacking about duration. The registry represents the largest dataset to date detailing these persistent skin symptoms and offers insight about how COVID-19 can affect many different organ systems even after patients recover from acute infection, Dr. Freeman said.
Eight different types of skin rashes were noted in the study group, of which 303 were lab-confirmed or suspected COVID-19 patients with skin symptoms. Of those, 224 total cases and 90 lab-confirmed cases included information on how long skin symptoms lasted. Lab tests for SARS-CoV-2 included polymerase chain reaction and serum antibody assays.
Dr. Freeman and associates defined “long-haulers” as patients with dermatologic symptoms of COVID-19 lasting 60 days or longer. These “outliers” are likely more prevalent than the registry suggests, she said, since not all providers initially reporting skin symptoms in patients updated that information over time.
“It’s important to understand that the registry is probably significantly underreporting the duration of symptoms and number of long-hauler patients,” she explained. “A registry is often a glimpse into a moment in time to these patients. To combat that, we followed up by email twice with providers to ask if patients’ symptoms were still ongoing or completed.”
Results showed a wide spectrum in average duration of symptoms among lab-confirmed COVID-19 patients, depending on specific rash. Urticaria lasted for a median of 4 days; morbilliform eruptions, 7 days; pernio/chilblains, 10 days; and papulosquamous eruptions, 20 days, with one long-hauler case lasting 70 days.
Five patients with pernio/chilblains were long-haulers, with toe symptoms enduring 60 days or longer. Only one went beyond 133 days with severe pernio and fatigue.
“The fact that we’re not necessarily seeing these long-hauler symptoms across every type of skin rash makes sense,” Dr. Freeman said. “Hives, for example, usually comes on acutely and leaves pretty rapidly. There are no reports of long-hauler hives.”
“That we’re really seeing these long-hauler symptoms in certain skin rashes really suggests that there’s a certain pathophysiology going in within that group of patients,” she added.
Dr. Freeman said not enough data have yet been generated to correlate long-standing COVID-19 skin symptoms with lasting cardiac, neurologic, or other symptoms of prolonged inflammation stemming from the virus.
Meanwhile, an EADV survey of 490 dermatologists revealed that just over one-third have seen patients presenting with skin signs of COVID-19. Moreover, 4% of dermatologists themselves tested positive for the virus.
Dr. Freeman encouraged all frontline clinicians assessing COVID-19 patients with skin symptoms to enter patients into the registry. But despite its strengths, the registry “can’t tell us what percentage of everyone who gets COVID will develop a skin finding or what percentage will be a long-hauler,” she said.
“A registry doesn’t have a denominator, so it’s like a giant case series,” she added.
“It will be very helpful going forward, as many places around the world experience second or third waves of COVID-19, to follow patients prospectively, acknowledge that patients will have symptoms lasting different amounts of time, and be aware these symptoms can occur on the skin,” she said.
Christopher Griffiths, MD, of the University of Manchester (England), praised the international registry as a valuable tool that will help clinicians better manage patients with COVID-19–related skin effects and predict prognosis.
“This has really brought the international dermatology community together, working on a focused goal relevant to all of us around the world,” Dr. Griffiths said in an interview. “It shows the power of communication and collaboration and what can be achieved in a short period of time.”
Dr. Freeman and Dr. Griffiths disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM THE EADV CONGRESS