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Lab Tests Are Key for Diagnosing Chickenpox
, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.
Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
Minnesota Offers Free Tests
In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.
MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.
The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).
During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
Clinical Diagnosis Versus Lab Test Confirmation
The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.
The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.
They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.
“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
Presentation May Also Be Different in Immunocompromised
Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.
In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.
Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.
Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”
But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.
The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.
, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.
Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
Minnesota Offers Free Tests
In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.
MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.
The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).
During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
Clinical Diagnosis Versus Lab Test Confirmation
The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.
The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.
They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.
“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
Presentation May Also Be Different in Immunocompromised
Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.
In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.
Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.
Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”
But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.
The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.
, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.
Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
Minnesota Offers Free Tests
In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.
MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.
The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).
During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
Clinical Diagnosis Versus Lab Test Confirmation
The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.
The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.
They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.
“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
Presentation May Also Be Different in Immunocompromised
Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.
In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.
Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.
Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”
But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.
The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.
FROM MMWR
Common Household Chemicals Tied to Brain Cell Damage
Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn.
Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland.
“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.
The results were published online on March 25 in Nature Neuroscience.
Motor Dysfunction
Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells.
The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.
They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.
In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).
After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).
Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2).
“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.
“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said.
In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
Too Soon to Tell
Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research.
“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said.
“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned.
“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said.
Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.
“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.
“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added.
The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures.
A version of this article appeared on Medscape.com.
Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn.
Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland.
“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.
The results were published online on March 25 in Nature Neuroscience.
Motor Dysfunction
Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells.
The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.
They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.
In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).
After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).
Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2).
“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.
“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said.
In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
Too Soon to Tell
Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research.
“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said.
“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned.
“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said.
Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.
“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.
“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added.
The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures.
A version of this article appeared on Medscape.com.
Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn.
Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland.
“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.
The results were published online on March 25 in Nature Neuroscience.
Motor Dysfunction
Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells.
The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.
They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.
In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).
After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).
Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2).
“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.
“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said.
In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
Too Soon to Tell
Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research.
“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said.
“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned.
“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said.
Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.
“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.
“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added.
The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures.
A version of this article appeared on Medscape.com.
Infant Exposure to MS Drugs via Breastfeeding: New Data
, new research confirmed.
Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.
“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.
“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Registry Data and Analysis
Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).
Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).
Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.
The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.
In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.
A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
‘Reassuring’ Data
Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”
Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”
“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.
“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”
In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.
The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research confirmed.
Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.
“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.
“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Registry Data and Analysis
Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).
Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).
Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.
The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.
In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.
A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
‘Reassuring’ Data
Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”
Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”
“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.
“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”
In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.
The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research confirmed.
Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.
“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.
“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Registry Data and Analysis
Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).
Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).
Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.
The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.
In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.
A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
‘Reassuring’ Data
Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”
Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”
“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.
“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”
In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.
The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.
A version of this article appeared on Medscape.com.
Few Childhood Cancer Survivors Get Recommended Screenings
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
PIK3CA-Related Overgrowth Spectrum (PROS): 5 Things to Know
PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.
Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.
The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.
Here are five things to know about PROS.
1. PROS comprises a heterogeneous group of rare congenital diseases.
PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.
PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:
- Fibroadipose hyperplasia (also called fibroadipose overgrowth)
- CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
- Klippel-Trenaunay syndrome
- Megalencephaly-capillary malformation (MCAP) syndrome
- Hemihyperplasia‐multiple lipomatosis syndrome
- Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
- Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
- Macrodactyly
- Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
- CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)
The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.
2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.
The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:
- Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
- Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
- Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
- Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
- Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
- Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
- Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.
3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.
Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.
The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.
Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.
4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.
PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).
This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.
This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.
5. Regular surveillance is crucial for the effective management of PROS
Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.
Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.
Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.
Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.
In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.
Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.
These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.
Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.
Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.
The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.
Here are five things to know about PROS.
1. PROS comprises a heterogeneous group of rare congenital diseases.
PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.
PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:
- Fibroadipose hyperplasia (also called fibroadipose overgrowth)
- CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
- Klippel-Trenaunay syndrome
- Megalencephaly-capillary malformation (MCAP) syndrome
- Hemihyperplasia‐multiple lipomatosis syndrome
- Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
- Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
- Macrodactyly
- Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
- CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)
The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.
2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.
The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:
- Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
- Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
- Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
- Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
- Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
- Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
- Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.
3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.
Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.
The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.
Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.
4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.
PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).
This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.
This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.
5. Regular surveillance is crucial for the effective management of PROS
Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.
Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.
Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.
Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.
In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.
Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.
These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.
Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.
Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.
The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.
Here are five things to know about PROS.
1. PROS comprises a heterogeneous group of rare congenital diseases.
PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.
PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:
- Fibroadipose hyperplasia (also called fibroadipose overgrowth)
- CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
- Klippel-Trenaunay syndrome
- Megalencephaly-capillary malformation (MCAP) syndrome
- Hemihyperplasia‐multiple lipomatosis syndrome
- Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
- Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
- Macrodactyly
- Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
- CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)
The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.
2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.
The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:
- Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
- Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
- Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
- Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
- Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
- Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
- Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.
3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.
Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.
The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.
Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.
4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.
PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).
This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.
This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.
5. Regular surveillance is crucial for the effective management of PROS
Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.
Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.
Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.
Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.
In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.
Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.
These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.
Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Measles Control So Far in 2024: ‘Not Off to a Great Start’
Just over 2 months into 2024, measles cases in the United States aren’t looking great.
The recent rise in cases across the U.S. is linked to unvaccinated travelers, lower than ideal vaccination rates, and misinformation, experts said.
The Centers for Disease Control and Prevention has identified 45 cases of measles in 17 jurisdictions across the U.S. As of March 7, the federal health agency reported measles cases in Arizona, California, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Michigan, Minnesota, Missouri, New Jersey, New York City, Ohio, Pennsylvania, Virginia, and Washington.
As for the 45 cases, “that’s almost as many as we had for the entire calendar year of 2023,” said Sarah Lim, MD, a medical specialist at the Minnesota Department of Health. “So we’re really not off to a great start.” (For context, there were 58 officially reported measles cases last year.)
Chicago is having a measles outbreak — with eight cases reported so far. All but one case has been linked to a migrant child at a city shelter. Given the potential for rapid spread — measles is relatively rare here but potentially very serious — the CDC sent a team of experts to investigate and to help keep this outbreak from growing further.
Sometimes Deadly
About 30% of children have measles symptoms and about 25% end up hospitalized. Complications include diarrhea, a whole-body rash, ear infections that can lead to permanent deafness, and pneumonia. Pneumonia with measles can be so serious that 1 in 20 affected children die. Measles can also cause inflammation of the brain called encephalitis in about 1 in 1,000 children, sometimes causing epilepsy or permanent brain damage.
As with long COVID, some effects can last beyond the early infection. For example, measles “can wipe out immune memory that protects you against other bacterial and viral pathogens,” Dr. Lim said at a media briefing sponsored by the Infectious Diseases Society of America. This vulnerability to other infections can last up to 3 years after the early infection, she noted.
Overall, measles kills between 1 and 3 people infected per thousand, mostly children.
Vaccine Misinformation Playing a Role
Vaccine misinformation is partly behind the uptick, and while many cases are mild, “this can be a devastating disease,” said Joshua Barocas, MD, associate professor of medicine in the divisions of General Internal Medicine and Infectious Diseases at the University of Colorado School of Medicine.
“I’m a parent myself. Parents are flooded with tons of information, some of that time being misinformation,” he said at the media briefing. “If you are a parent who’s been on the fence [about vaccination], now is the time, given the outbreak potential and the outbreaks that we’re seeing.”
Vaccine misinformation “is about as old as vaccines themselves,” Dr. Lim said. Concerns about the MMR vaccine, which includes measles protection, are not new.
“It does seem to change periodically — new things bubble up, new ideas bubble up, and the problem is that it is like the old saying that ‘a lie can get halfway around the world before the truth can get its boots on.’ ” Social media helps to amplify vaccine misinformation, she said.
“You don’t want to scare people unnecessarily — but reminding people what these childhood diseases really look like and what they do is incredibly important,” Dr. Lim said. “It’s so much easier to see stories about potential side effects of vaccines than it is to see stories about parents whose children were in intensive care for 2 weeks with pneumonia because of a severe case of measles.”
Dr. Barocas said misinformation is sometimes deliberate, sometimes not. Regardless, “our job as infectious disease physicians and public health professionals is not necessarily to put the counternarrative out there, but to continue to advocate for what we know works based on the best science and the best evidence.”
“And there is no reason to believe that vaccines are anything but helpful when it comes to preventing measles,” he noted.
Lifelong Protection in Most Cases
The MMR vaccine, typically given as two doses in childhood, offers 93% and then 97% protection against the highly contagious virus. During the 2022-to-2023 school year, the measles vaccination rate among kindergarten children nationwide was 92%. That sounds like a high rate, Dr. Lim said, “but because measles is so contagious, vaccination rates need to be 95% or higher to contain transmission.”
One person with measles can infect anywhere from 12 to 18 other people, she said. When an infected person coughs or sneezes, tiny droplets spread through the air. “And if someone is unvaccinated and exposed, 9 times out of 10, that person will go on to develop the disease.” She said given the high transmission rate, measles often spreads within families to infect multiple children.
If you know you’re not vaccinated but exposed, the advice is to get the measles shot as quickly as possible. “There is a recommendation to receive the MMR vaccine within 72 hours as post-exposure prophylaxis,” Dr. Lim said. “That’s a tight time window, but if you can do that, it reduces the risk of developing measles significantly.”
If you’re unsure or do not remember getting vaccinated against measles as a young child, your health care provider may be able to search state registries for an answer. If that doesn’t work, getting revaccinated with the MMR vaccine as an adult is an option. “There is no shame in getting caught up now,” Dr. Barocas said.
Dr. Lim agreed. “There is really no downside to getting additional doses.”
A version of this article appeared on WebMD.com.
Just over 2 months into 2024, measles cases in the United States aren’t looking great.
The recent rise in cases across the U.S. is linked to unvaccinated travelers, lower than ideal vaccination rates, and misinformation, experts said.
The Centers for Disease Control and Prevention has identified 45 cases of measles in 17 jurisdictions across the U.S. As of March 7, the federal health agency reported measles cases in Arizona, California, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Michigan, Minnesota, Missouri, New Jersey, New York City, Ohio, Pennsylvania, Virginia, and Washington.
As for the 45 cases, “that’s almost as many as we had for the entire calendar year of 2023,” said Sarah Lim, MD, a medical specialist at the Minnesota Department of Health. “So we’re really not off to a great start.” (For context, there were 58 officially reported measles cases last year.)
Chicago is having a measles outbreak — with eight cases reported so far. All but one case has been linked to a migrant child at a city shelter. Given the potential for rapid spread — measles is relatively rare here but potentially very serious — the CDC sent a team of experts to investigate and to help keep this outbreak from growing further.
Sometimes Deadly
About 30% of children have measles symptoms and about 25% end up hospitalized. Complications include diarrhea, a whole-body rash, ear infections that can lead to permanent deafness, and pneumonia. Pneumonia with measles can be so serious that 1 in 20 affected children die. Measles can also cause inflammation of the brain called encephalitis in about 1 in 1,000 children, sometimes causing epilepsy or permanent brain damage.
As with long COVID, some effects can last beyond the early infection. For example, measles “can wipe out immune memory that protects you against other bacterial and viral pathogens,” Dr. Lim said at a media briefing sponsored by the Infectious Diseases Society of America. This vulnerability to other infections can last up to 3 years after the early infection, she noted.
Overall, measles kills between 1 and 3 people infected per thousand, mostly children.
Vaccine Misinformation Playing a Role
Vaccine misinformation is partly behind the uptick, and while many cases are mild, “this can be a devastating disease,” said Joshua Barocas, MD, associate professor of medicine in the divisions of General Internal Medicine and Infectious Diseases at the University of Colorado School of Medicine.
“I’m a parent myself. Parents are flooded with tons of information, some of that time being misinformation,” he said at the media briefing. “If you are a parent who’s been on the fence [about vaccination], now is the time, given the outbreak potential and the outbreaks that we’re seeing.”
Vaccine misinformation “is about as old as vaccines themselves,” Dr. Lim said. Concerns about the MMR vaccine, which includes measles protection, are not new.
“It does seem to change periodically — new things bubble up, new ideas bubble up, and the problem is that it is like the old saying that ‘a lie can get halfway around the world before the truth can get its boots on.’ ” Social media helps to amplify vaccine misinformation, she said.
“You don’t want to scare people unnecessarily — but reminding people what these childhood diseases really look like and what they do is incredibly important,” Dr. Lim said. “It’s so much easier to see stories about potential side effects of vaccines than it is to see stories about parents whose children were in intensive care for 2 weeks with pneumonia because of a severe case of measles.”
Dr. Barocas said misinformation is sometimes deliberate, sometimes not. Regardless, “our job as infectious disease physicians and public health professionals is not necessarily to put the counternarrative out there, but to continue to advocate for what we know works based on the best science and the best evidence.”
“And there is no reason to believe that vaccines are anything but helpful when it comes to preventing measles,” he noted.
Lifelong Protection in Most Cases
The MMR vaccine, typically given as two doses in childhood, offers 93% and then 97% protection against the highly contagious virus. During the 2022-to-2023 school year, the measles vaccination rate among kindergarten children nationwide was 92%. That sounds like a high rate, Dr. Lim said, “but because measles is so contagious, vaccination rates need to be 95% or higher to contain transmission.”
One person with measles can infect anywhere from 12 to 18 other people, she said. When an infected person coughs or sneezes, tiny droplets spread through the air. “And if someone is unvaccinated and exposed, 9 times out of 10, that person will go on to develop the disease.” She said given the high transmission rate, measles often spreads within families to infect multiple children.
If you know you’re not vaccinated but exposed, the advice is to get the measles shot as quickly as possible. “There is a recommendation to receive the MMR vaccine within 72 hours as post-exposure prophylaxis,” Dr. Lim said. “That’s a tight time window, but if you can do that, it reduces the risk of developing measles significantly.”
If you’re unsure or do not remember getting vaccinated against measles as a young child, your health care provider may be able to search state registries for an answer. If that doesn’t work, getting revaccinated with the MMR vaccine as an adult is an option. “There is no shame in getting caught up now,” Dr. Barocas said.
Dr. Lim agreed. “There is really no downside to getting additional doses.”
A version of this article appeared on WebMD.com.
Just over 2 months into 2024, measles cases in the United States aren’t looking great.
The recent rise in cases across the U.S. is linked to unvaccinated travelers, lower than ideal vaccination rates, and misinformation, experts said.
The Centers for Disease Control and Prevention has identified 45 cases of measles in 17 jurisdictions across the U.S. As of March 7, the federal health agency reported measles cases in Arizona, California, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Michigan, Minnesota, Missouri, New Jersey, New York City, Ohio, Pennsylvania, Virginia, and Washington.
As for the 45 cases, “that’s almost as many as we had for the entire calendar year of 2023,” said Sarah Lim, MD, a medical specialist at the Minnesota Department of Health. “So we’re really not off to a great start.” (For context, there were 58 officially reported measles cases last year.)
Chicago is having a measles outbreak — with eight cases reported so far. All but one case has been linked to a migrant child at a city shelter. Given the potential for rapid spread — measles is relatively rare here but potentially very serious — the CDC sent a team of experts to investigate and to help keep this outbreak from growing further.
Sometimes Deadly
About 30% of children have measles symptoms and about 25% end up hospitalized. Complications include diarrhea, a whole-body rash, ear infections that can lead to permanent deafness, and pneumonia. Pneumonia with measles can be so serious that 1 in 20 affected children die. Measles can also cause inflammation of the brain called encephalitis in about 1 in 1,000 children, sometimes causing epilepsy or permanent brain damage.
As with long COVID, some effects can last beyond the early infection. For example, measles “can wipe out immune memory that protects you against other bacterial and viral pathogens,” Dr. Lim said at a media briefing sponsored by the Infectious Diseases Society of America. This vulnerability to other infections can last up to 3 years after the early infection, she noted.
Overall, measles kills between 1 and 3 people infected per thousand, mostly children.
Vaccine Misinformation Playing a Role
Vaccine misinformation is partly behind the uptick, and while many cases are mild, “this can be a devastating disease,” said Joshua Barocas, MD, associate professor of medicine in the divisions of General Internal Medicine and Infectious Diseases at the University of Colorado School of Medicine.
“I’m a parent myself. Parents are flooded with tons of information, some of that time being misinformation,” he said at the media briefing. “If you are a parent who’s been on the fence [about vaccination], now is the time, given the outbreak potential and the outbreaks that we’re seeing.”
Vaccine misinformation “is about as old as vaccines themselves,” Dr. Lim said. Concerns about the MMR vaccine, which includes measles protection, are not new.
“It does seem to change periodically — new things bubble up, new ideas bubble up, and the problem is that it is like the old saying that ‘a lie can get halfway around the world before the truth can get its boots on.’ ” Social media helps to amplify vaccine misinformation, she said.
“You don’t want to scare people unnecessarily — but reminding people what these childhood diseases really look like and what they do is incredibly important,” Dr. Lim said. “It’s so much easier to see stories about potential side effects of vaccines than it is to see stories about parents whose children were in intensive care for 2 weeks with pneumonia because of a severe case of measles.”
Dr. Barocas said misinformation is sometimes deliberate, sometimes not. Regardless, “our job as infectious disease physicians and public health professionals is not necessarily to put the counternarrative out there, but to continue to advocate for what we know works based on the best science and the best evidence.”
“And there is no reason to believe that vaccines are anything but helpful when it comes to preventing measles,” he noted.
Lifelong Protection in Most Cases
The MMR vaccine, typically given as two doses in childhood, offers 93% and then 97% protection against the highly contagious virus. During the 2022-to-2023 school year, the measles vaccination rate among kindergarten children nationwide was 92%. That sounds like a high rate, Dr. Lim said, “but because measles is so contagious, vaccination rates need to be 95% or higher to contain transmission.”
One person with measles can infect anywhere from 12 to 18 other people, she said. When an infected person coughs or sneezes, tiny droplets spread through the air. “And if someone is unvaccinated and exposed, 9 times out of 10, that person will go on to develop the disease.” She said given the high transmission rate, measles often spreads within families to infect multiple children.
If you know you’re not vaccinated but exposed, the advice is to get the measles shot as quickly as possible. “There is a recommendation to receive the MMR vaccine within 72 hours as post-exposure prophylaxis,” Dr. Lim said. “That’s a tight time window, but if you can do that, it reduces the risk of developing measles significantly.”
If you’re unsure or do not remember getting vaccinated against measles as a young child, your health care provider may be able to search state registries for an answer. If that doesn’t work, getting revaccinated with the MMR vaccine as an adult is an option. “There is no shame in getting caught up now,” Dr. Barocas said.
Dr. Lim agreed. “There is really no downside to getting additional doses.”
A version of this article appeared on WebMD.com.
Benzene Detected in Benzoyl Peroxide Products: Debate On Implications Continues
Nine days after the independent laboratory, it published another report in Environmental Health Perspectives (EHP), on March 14, also warning about BP acne products.
The bottom line was the same: The laboratory, based in New Haven, Connecticut, said its analyses raise substantial concerns about the safety of BP-containing acne products currently on the market.
The lab’s results showed that the products can form over 800 times the conditionally restricted FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter products affected.
“This is a problem of degradation, not contamination,” David Light, CEO and founder of Valisure, said in a telephone interview. BP can decompose into benzene, and exposure to benzene has been linked with a higher risk for leukemia and other blood cancers, according to the American Cancer Society.
In the wake of the findings, however, debate has erupted over the method and approach used by Valisure to test these products, with critics and companies contending that more “real-world” use data are needed. And the US Pharmacopeia (USP) is asking for full transparency about the testing methods.
In a March 8 statement, USP said the petition indicated that modified USP methods were used in the study, noting that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”
However, Valisure contended that drug products need to demonstrate stability over the entire life cycle, from shipment to continued use, emphasizing that constitutes the best “real-world” approach. It also defended the methodology it used.
The reports have led to a state of uncertainty about the use of BP products.
“Right now, we have more unknowns than anything else,” John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a video posted on X and YouTube, summarizing the findings released by Valisure on March 6 and 14. He was not involved in the Valisure research.
In a telephone interview, Dr. Barbieri said the report “needs to be taken seriously,” but he also believed the Valisure report is lacking information about testing under “real-world” conditions. He is calling for more information and more transparency about the data. What’s clear, Dr. Barbieri told this news organization, is that the findings about high benzene levels are not a manufacturing error. “It’s something to do with the molecule itself.”
Valisure’s Analyses
Valisure performed an initial analysis, using a method called gas chromatography-mass spectrometry, which is the FDA-preferred method for detecting benzene, Mr. Light said. It tested 175 acne products, 99 containing BP and 76 with other ingredients, such as salicylic acid. All the products without BP had no detectable benzene or values below 2 ppm, the FDA concentration limit for benzene.
Of the 99 BP products, 94 contained benzene without any elevated temperature incubation, according to Valisure. Using 50 °C (122 °F, the accepted pharmaceutical stability testing temperature) on 66 products, Valisure detected over 1500 ppm of benzene in two products, over 100 ppm in 17 products, and over 10 ppm in 42 products over an 18-day period.
The analysis confirmed, Valisure said in a press release and the petition, that a substantial amount of benzene can form in a BP product and leak outside the packaging into surrounding air.
The EHP paper, which includes authors from Valisure, reported that researchers took single lots of seven branded BP products, namely, Equate Beauty 2.5% BP cleansers, Neutrogena 10% BP cleanser, CVS Health 10% BP face wash, Walgreens 10% BP cream, Clean & Clear 10% cleanser, Equate Beauty 10% BP acne wash, and Proactiv 2.5% BP cleanser.
Using testing that involved gas chromatography-mass spectrometry, benzene was detected in all the BP products samples tested, and levels increased during incubation at body and shelf-life performance temperatures to more than 2 ppm. The authors concluded that the study “raises substantial concerns” about the safety of BP products currently on the market.
Methodology Debates
Two days after Valisure released its analysis on March 6, the USP reviewed the citizen’s petition filed by Valisure and called for more transparency around the testing methods.
“The petition referenced USP and indicated that modified USP methods and procedures were used in the study. The presence of unsafe levels of benzene should be taken seriously,” the statement said. The USP statement also noted that the Valisure analysis used modified USP methods and said that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”
In its statement, USP took issue with a practice known as accelerated thermal degradation, which it said Valisure used. USP said the approach involves raising the storage temperature of a product to higher than the temperature indicated on the label for the purpose of simulating degradation over a longer period. While the approach may be acceptable, USP said, the temperatures chosen may not be what is expected to happen to the products.
In response, Mr. Light of Valisure referenced guidance issued in August, 2020, from the FDA, stating that the method it used in the BP analysis can be used to detect impurities in hand sanitizers, including benzene. (In 2021, Valisure detected high levels of benzene in some hand sanitizers and asked the FDA to take action.)
Company Response
Among the companies that took issue with the report was Reckitt, which makes Clearasil, which contains BP. In a statement, the company said, in part: “The products and their ingredients are stable over the storage conditions described on their packaging which represent all reasonable and foreseeable conditions.” It said the findings presented by Valisure reflect “unrealistic scenarios rather than real-world conditions.”
The Personal Care Products Council, a national trade association that represents cosmetic and personal care product manufacturers, also took issue with the findings and the approach used to evaluate the products.
FDA and the Citizen’s Petition
The FDA accepted the petition, Mr. Light said, and gave it a docket number. “We’ll hopefully hear more soon” because the FDA is required to respond to a citizen’s petition within 180 days, he said.
“We generally don’t comment on pending citizens’ petitions,” an FDA spokesperson said in an email. “When we respond, we will respond directly to the petitioner and post the response in the designated agency public docket.”
Valisure’s Patent Application
Mr. Light and others have applied for a patent on methods of producing shelf-stable formulations to prevent degradation of BP to benzene.
“We saw the problem long before we had any sort of application,” Mr. Light said. The issue has been “known for decades.”
Role of BP Products for Acne
In the midst of uncertainty, “the first discussion is, do we want to use it?” Dr. Barbieri said in the interview. Some patients may want to avoid it altogether, until more data are available, including more verification of the findings, while others may be comfortable accepting the potential risk, he said.
“Benzoyl peroxide is one of our foundational acne treatments,” Dr. Barbieri said. In the American Academy of Dermatology updated guidelines on acne, published in January, 2024, strong recommendations were made for BP products, as well as topical retinoids, topical antibiotics, and oral doxycycline.
“When you take away BP, there’s no substitute for it,” Dr. Barbieri said. And if patients don’t get improvement with topicals, oral medications might be needed, and “these all have their own risks.”
In the Interim
Until more information is available, Dr. Barbieri is advising patients not to store the products at high temperatures or for a long time. Don’t keep the products past their expiration date, and perhaps keep products for a shorter time, “something like a month,” he said.
Those living in a hot climate might consider storing the products in the refrigerator, he said.
“We need more data from Valisure, from other groups that confirm their findings, and we need to hear from the FDA,” Dr. Barbieri said. “There’s a lot of uncertainty right now. But it’s important not to overreact.”
Dr. Barbieri had no relevant disclosures.
A version of this article appeared on Medscape.com.
Nine days after the independent laboratory, it published another report in Environmental Health Perspectives (EHP), on March 14, also warning about BP acne products.
The bottom line was the same: The laboratory, based in New Haven, Connecticut, said its analyses raise substantial concerns about the safety of BP-containing acne products currently on the market.
The lab’s results showed that the products can form over 800 times the conditionally restricted FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter products affected.
“This is a problem of degradation, not contamination,” David Light, CEO and founder of Valisure, said in a telephone interview. BP can decompose into benzene, and exposure to benzene has been linked with a higher risk for leukemia and other blood cancers, according to the American Cancer Society.
In the wake of the findings, however, debate has erupted over the method and approach used by Valisure to test these products, with critics and companies contending that more “real-world” use data are needed. And the US Pharmacopeia (USP) is asking for full transparency about the testing methods.
In a March 8 statement, USP said the petition indicated that modified USP methods were used in the study, noting that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”
However, Valisure contended that drug products need to demonstrate stability over the entire life cycle, from shipment to continued use, emphasizing that constitutes the best “real-world” approach. It also defended the methodology it used.
The reports have led to a state of uncertainty about the use of BP products.
“Right now, we have more unknowns than anything else,” John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a video posted on X and YouTube, summarizing the findings released by Valisure on March 6 and 14. He was not involved in the Valisure research.
In a telephone interview, Dr. Barbieri said the report “needs to be taken seriously,” but he also believed the Valisure report is lacking information about testing under “real-world” conditions. He is calling for more information and more transparency about the data. What’s clear, Dr. Barbieri told this news organization, is that the findings about high benzene levels are not a manufacturing error. “It’s something to do with the molecule itself.”
Valisure’s Analyses
Valisure performed an initial analysis, using a method called gas chromatography-mass spectrometry, which is the FDA-preferred method for detecting benzene, Mr. Light said. It tested 175 acne products, 99 containing BP and 76 with other ingredients, such as salicylic acid. All the products without BP had no detectable benzene or values below 2 ppm, the FDA concentration limit for benzene.
Of the 99 BP products, 94 contained benzene without any elevated temperature incubation, according to Valisure. Using 50 °C (122 °F, the accepted pharmaceutical stability testing temperature) on 66 products, Valisure detected over 1500 ppm of benzene in two products, over 100 ppm in 17 products, and over 10 ppm in 42 products over an 18-day period.
The analysis confirmed, Valisure said in a press release and the petition, that a substantial amount of benzene can form in a BP product and leak outside the packaging into surrounding air.
The EHP paper, which includes authors from Valisure, reported that researchers took single lots of seven branded BP products, namely, Equate Beauty 2.5% BP cleansers, Neutrogena 10% BP cleanser, CVS Health 10% BP face wash, Walgreens 10% BP cream, Clean & Clear 10% cleanser, Equate Beauty 10% BP acne wash, and Proactiv 2.5% BP cleanser.
Using testing that involved gas chromatography-mass spectrometry, benzene was detected in all the BP products samples tested, and levels increased during incubation at body and shelf-life performance temperatures to more than 2 ppm. The authors concluded that the study “raises substantial concerns” about the safety of BP products currently on the market.
Methodology Debates
Two days after Valisure released its analysis on March 6, the USP reviewed the citizen’s petition filed by Valisure and called for more transparency around the testing methods.
“The petition referenced USP and indicated that modified USP methods and procedures were used in the study. The presence of unsafe levels of benzene should be taken seriously,” the statement said. The USP statement also noted that the Valisure analysis used modified USP methods and said that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”
In its statement, USP took issue with a practice known as accelerated thermal degradation, which it said Valisure used. USP said the approach involves raising the storage temperature of a product to higher than the temperature indicated on the label for the purpose of simulating degradation over a longer period. While the approach may be acceptable, USP said, the temperatures chosen may not be what is expected to happen to the products.
In response, Mr. Light of Valisure referenced guidance issued in August, 2020, from the FDA, stating that the method it used in the BP analysis can be used to detect impurities in hand sanitizers, including benzene. (In 2021, Valisure detected high levels of benzene in some hand sanitizers and asked the FDA to take action.)
Company Response
Among the companies that took issue with the report was Reckitt, which makes Clearasil, which contains BP. In a statement, the company said, in part: “The products and their ingredients are stable over the storage conditions described on their packaging which represent all reasonable and foreseeable conditions.” It said the findings presented by Valisure reflect “unrealistic scenarios rather than real-world conditions.”
The Personal Care Products Council, a national trade association that represents cosmetic and personal care product manufacturers, also took issue with the findings and the approach used to evaluate the products.
FDA and the Citizen’s Petition
The FDA accepted the petition, Mr. Light said, and gave it a docket number. “We’ll hopefully hear more soon” because the FDA is required to respond to a citizen’s petition within 180 days, he said.
“We generally don’t comment on pending citizens’ petitions,” an FDA spokesperson said in an email. “When we respond, we will respond directly to the petitioner and post the response in the designated agency public docket.”
Valisure’s Patent Application
Mr. Light and others have applied for a patent on methods of producing shelf-stable formulations to prevent degradation of BP to benzene.
“We saw the problem long before we had any sort of application,” Mr. Light said. The issue has been “known for decades.”
Role of BP Products for Acne
In the midst of uncertainty, “the first discussion is, do we want to use it?” Dr. Barbieri said in the interview. Some patients may want to avoid it altogether, until more data are available, including more verification of the findings, while others may be comfortable accepting the potential risk, he said.
“Benzoyl peroxide is one of our foundational acne treatments,” Dr. Barbieri said. In the American Academy of Dermatology updated guidelines on acne, published in January, 2024, strong recommendations were made for BP products, as well as topical retinoids, topical antibiotics, and oral doxycycline.
“When you take away BP, there’s no substitute for it,” Dr. Barbieri said. And if patients don’t get improvement with topicals, oral medications might be needed, and “these all have their own risks.”
In the Interim
Until more information is available, Dr. Barbieri is advising patients not to store the products at high temperatures or for a long time. Don’t keep the products past their expiration date, and perhaps keep products for a shorter time, “something like a month,” he said.
Those living in a hot climate might consider storing the products in the refrigerator, he said.
“We need more data from Valisure, from other groups that confirm their findings, and we need to hear from the FDA,” Dr. Barbieri said. “There’s a lot of uncertainty right now. But it’s important not to overreact.”
Dr. Barbieri had no relevant disclosures.
A version of this article appeared on Medscape.com.
Nine days after the independent laboratory, it published another report in Environmental Health Perspectives (EHP), on March 14, also warning about BP acne products.
The bottom line was the same: The laboratory, based in New Haven, Connecticut, said its analyses raise substantial concerns about the safety of BP-containing acne products currently on the market.
The lab’s results showed that the products can form over 800 times the conditionally restricted FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter products affected.
“This is a problem of degradation, not contamination,” David Light, CEO and founder of Valisure, said in a telephone interview. BP can decompose into benzene, and exposure to benzene has been linked with a higher risk for leukemia and other blood cancers, according to the American Cancer Society.
In the wake of the findings, however, debate has erupted over the method and approach used by Valisure to test these products, with critics and companies contending that more “real-world” use data are needed. And the US Pharmacopeia (USP) is asking for full transparency about the testing methods.
In a March 8 statement, USP said the petition indicated that modified USP methods were used in the study, noting that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”
However, Valisure contended that drug products need to demonstrate stability over the entire life cycle, from shipment to continued use, emphasizing that constitutes the best “real-world” approach. It also defended the methodology it used.
The reports have led to a state of uncertainty about the use of BP products.
“Right now, we have more unknowns than anything else,” John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a video posted on X and YouTube, summarizing the findings released by Valisure on March 6 and 14. He was not involved in the Valisure research.
In a telephone interview, Dr. Barbieri said the report “needs to be taken seriously,” but he also believed the Valisure report is lacking information about testing under “real-world” conditions. He is calling for more information and more transparency about the data. What’s clear, Dr. Barbieri told this news organization, is that the findings about high benzene levels are not a manufacturing error. “It’s something to do with the molecule itself.”
Valisure’s Analyses
Valisure performed an initial analysis, using a method called gas chromatography-mass spectrometry, which is the FDA-preferred method for detecting benzene, Mr. Light said. It tested 175 acne products, 99 containing BP and 76 with other ingredients, such as salicylic acid. All the products without BP had no detectable benzene or values below 2 ppm, the FDA concentration limit for benzene.
Of the 99 BP products, 94 contained benzene without any elevated temperature incubation, according to Valisure. Using 50 °C (122 °F, the accepted pharmaceutical stability testing temperature) on 66 products, Valisure detected over 1500 ppm of benzene in two products, over 100 ppm in 17 products, and over 10 ppm in 42 products over an 18-day period.
The analysis confirmed, Valisure said in a press release and the petition, that a substantial amount of benzene can form in a BP product and leak outside the packaging into surrounding air.
The EHP paper, which includes authors from Valisure, reported that researchers took single lots of seven branded BP products, namely, Equate Beauty 2.5% BP cleansers, Neutrogena 10% BP cleanser, CVS Health 10% BP face wash, Walgreens 10% BP cream, Clean & Clear 10% cleanser, Equate Beauty 10% BP acne wash, and Proactiv 2.5% BP cleanser.
Using testing that involved gas chromatography-mass spectrometry, benzene was detected in all the BP products samples tested, and levels increased during incubation at body and shelf-life performance temperatures to more than 2 ppm. The authors concluded that the study “raises substantial concerns” about the safety of BP products currently on the market.
Methodology Debates
Two days after Valisure released its analysis on March 6, the USP reviewed the citizen’s petition filed by Valisure and called for more transparency around the testing methods.
“The petition referenced USP and indicated that modified USP methods and procedures were used in the study. The presence of unsafe levels of benzene should be taken seriously,” the statement said. The USP statement also noted that the Valisure analysis used modified USP methods and said that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”
In its statement, USP took issue with a practice known as accelerated thermal degradation, which it said Valisure used. USP said the approach involves raising the storage temperature of a product to higher than the temperature indicated on the label for the purpose of simulating degradation over a longer period. While the approach may be acceptable, USP said, the temperatures chosen may not be what is expected to happen to the products.
In response, Mr. Light of Valisure referenced guidance issued in August, 2020, from the FDA, stating that the method it used in the BP analysis can be used to detect impurities in hand sanitizers, including benzene. (In 2021, Valisure detected high levels of benzene in some hand sanitizers and asked the FDA to take action.)
Company Response
Among the companies that took issue with the report was Reckitt, which makes Clearasil, which contains BP. In a statement, the company said, in part: “The products and their ingredients are stable over the storage conditions described on their packaging which represent all reasonable and foreseeable conditions.” It said the findings presented by Valisure reflect “unrealistic scenarios rather than real-world conditions.”
The Personal Care Products Council, a national trade association that represents cosmetic and personal care product manufacturers, also took issue with the findings and the approach used to evaluate the products.
FDA and the Citizen’s Petition
The FDA accepted the petition, Mr. Light said, and gave it a docket number. “We’ll hopefully hear more soon” because the FDA is required to respond to a citizen’s petition within 180 days, he said.
“We generally don’t comment on pending citizens’ petitions,” an FDA spokesperson said in an email. “When we respond, we will respond directly to the petitioner and post the response in the designated agency public docket.”
Valisure’s Patent Application
Mr. Light and others have applied for a patent on methods of producing shelf-stable formulations to prevent degradation of BP to benzene.
“We saw the problem long before we had any sort of application,” Mr. Light said. The issue has been “known for decades.”
Role of BP Products for Acne
In the midst of uncertainty, “the first discussion is, do we want to use it?” Dr. Barbieri said in the interview. Some patients may want to avoid it altogether, until more data are available, including more verification of the findings, while others may be comfortable accepting the potential risk, he said.
“Benzoyl peroxide is one of our foundational acne treatments,” Dr. Barbieri said. In the American Academy of Dermatology updated guidelines on acne, published in January, 2024, strong recommendations were made for BP products, as well as topical retinoids, topical antibiotics, and oral doxycycline.
“When you take away BP, there’s no substitute for it,” Dr. Barbieri said. And if patients don’t get improvement with topicals, oral medications might be needed, and “these all have their own risks.”
In the Interim
Until more information is available, Dr. Barbieri is advising patients not to store the products at high temperatures or for a long time. Don’t keep the products past their expiration date, and perhaps keep products for a shorter time, “something like a month,” he said.
Those living in a hot climate might consider storing the products in the refrigerator, he said.
“We need more data from Valisure, from other groups that confirm their findings, and we need to hear from the FDA,” Dr. Barbieri said. “There’s a lot of uncertainty right now. But it’s important not to overreact.”
Dr. Barbieri had no relevant disclosures.
A version of this article appeared on Medscape.com.
Is Melatonin a Valuable Resource or Children’s Health Risk?
For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.
To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.
“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”
Melatonin is sold without a prescription as a sleep aid in the form of a supplement.
Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.
Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.
Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.
The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.
Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.
“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
Almost 1 in 5 Children Use Melatonin
Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.
The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution.
“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
What’s the Best Way to Give Kids Melatonin?
Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm.
But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first.
“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”
Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said.
But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.
According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
Dangers of Keeping It Within Reach
One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children.
Because it is sold as a supplement, there are no child-safe packaging requirements.
“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”
She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.
“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
A version of this article appeared on WebMD.com.
For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.
To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.
“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”
Melatonin is sold without a prescription as a sleep aid in the form of a supplement.
Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.
Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.
Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.
The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.
Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.
“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
Almost 1 in 5 Children Use Melatonin
Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.
The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution.
“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
What’s the Best Way to Give Kids Melatonin?
Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm.
But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first.
“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”
Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said.
But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.
According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
Dangers of Keeping It Within Reach
One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children.
Because it is sold as a supplement, there are no child-safe packaging requirements.
“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”
She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.
“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
A version of this article appeared on WebMD.com.
For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.
To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.
“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”
Melatonin is sold without a prescription as a sleep aid in the form of a supplement.
Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.
Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.
Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.
The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.
Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.
“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
Almost 1 in 5 Children Use Melatonin
Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.
The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution.
“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
What’s the Best Way to Give Kids Melatonin?
Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm.
But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first.
“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”
Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said.
But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.
According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
Dangers of Keeping It Within Reach
One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children.
Because it is sold as a supplement, there are no child-safe packaging requirements.
“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”
She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.
“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
A version of this article appeared on WebMD.com.
Childhood Adversity Robustly Linked to Adult Mental Illness
Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.
Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.
The findings showed that the association held even after controlling for shared genetic and environmental factors.
The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.
The findings were published online on March 6 in JAMA Psychiatry.
Dose-Dependent Effect
Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.
To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.
The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.
The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.
Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.
Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.
More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.
At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
Untangling Genes and Environment
To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).
The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.
Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).
“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.
One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.
The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.
Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.
The findings showed that the association held even after controlling for shared genetic and environmental factors.
The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.
The findings were published online on March 6 in JAMA Psychiatry.
Dose-Dependent Effect
Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.
To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.
The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.
The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.
Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.
Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.
More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.
At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
Untangling Genes and Environment
To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).
The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.
Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).
“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.
One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.
The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.
Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.
The findings showed that the association held even after controlling for shared genetic and environmental factors.
The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.
The findings were published online on March 6 in JAMA Psychiatry.
Dose-Dependent Effect
Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.
To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.
The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.
The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.
Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.
Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.
More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.
At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
Untangling Genes and Environment
To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).
The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.
Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).
“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.
One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.
The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
Systematic Viral Testing in Emergency Departments Has Limited Benefit for General Population
Routine use of rapid respiratory virus testing in the emergency department (ED) appears to show limited benefit among patients with signs and symptoms of acute respiratory infection (ARI), according to a new study.
Rapid viral testing wasn’t associated with reduced antibiotic use, ED length of stay, or rates of ED return visits or hospitalization. However, testing was associated with a small increase in antiviral prescriptions and a small reduction in blood tests and chest x-rays.
“Our interest in studying the benefits of rapid viral testing in emergency departments comes from a commitment to diagnostic stewardship — ensuring that the right tests are administered to the right patients at the right time while also curbing overuse,” said lead author Tilmann Schober, MD, a resident in pediatric infectious disease at McGill University and Montreal Children’s Hospital.
“Following the SARS-CoV-2 pandemic, we have seen a surge in the availability of rapid viral testing, including molecular multiplex panels,” he said. “However, the actual impact of these advancements on patient care in the ED remains uncertain.”
The study was published online on March 4, 2024, in JAMA Internal Medicine).
Rapid Viral Testing
Dr. Schober and colleagues conducted a systematic review and meta-analysis of 11 randomized clinical trials to understand whether rapid testing for respiratory viruses was associated with patient treatment in the ED.
In particular, the research team looked at whether testing in patients with suspected ARI was associated with decreased antibiotic use, ancillary tests, ED length of stay, ED return visits, hospitalization, and increased influenza antiviral treatment.
Among the trials, seven studies included molecular testing, and eight used multiplex panels, including influenza and respiratory syncytial virus (RSV), influenza/RSV/adenovirus/parainfluenza, or a panel of 15 or more respiratory viruses. No study evaluated testing for SARS-CoV-2. The research team reported risk ratios (RRs) and risk difference estimates.
In general, routine rapid viral testing was associated with higher use of influenza antivirals (RR, 1.33) and lower use of chest radiography (RR, 0.88) and blood tests (RR, 0.81). However, the magnitude of these effects was small. For instance, to achieve one additional viral prescription, 70 patients would need to be tested, and to save one x-ray, 30 patients would need to be tested.
“This suggests that, while statistically significant, the practical impact of these secondary outcomes may not justify the extensive effort and resources involved in widespread testing,” Dr. Schober said.
In addition, there was no association between rapid testing and antibiotic use (RR, 0.99), urine testing (RR, 0.95), ED length of stay (0 h), return visits (RR, 0.93), or hospitalization (RR, 1.01).
Notably, there was no association between rapid viral testing and antibiotic use in any prespecified subgroup based on age, test method, publication date, number of viral targets, risk of bias, or industry funding, the authors said. They concluded that rapid virus testing should be reserved for patients for whom the testing will change treatment, such as high-risk patients or those with severe disease.
“It’s crucial to note that our study specifically evaluated the impact of systematic testing of patients with signs and symptoms of acute respiratory infection. Our findings do not advocate against rapid respiratory virus testing in general,” Dr. Schober said. “There is well-established evidence supporting the benefits of viral testing in certain contexts, such as hospitalized patients, to guide infection control practices or in specific high-risk populations.”
Future Research
Additional studies should look at testing among subgroups, particularly those with high-risk conditions, the study authors wrote. In addition, the research team would like to study the implementation of novel diagnostic stewardship programs as compared with well-established antibiotic stewardship programs.
“Acute respiratory tract illnesses represent one of the most common reasons for being evaluated in an acute care setting, especially in pediatrics, and these visits have traditionally resulted in excessive antibiotic prescribing, despite the etiology of the infection mostly being viral,” said Suchitra Rao, MBBS, associate professor of pediatrics at the University of Colorado School of Medicine and associate medical director of infection prevention and control at Children’s Hospital Colorado, Aurora.
Dr. Rao, who wasn’t involved with this study, has surveyed ED providers about respiratory viral testing and changes in clinical decision-making. She and colleagues found that providers most commonly changed clinical decision-making while prescribing an antiviral if influenza was detected or withholding antivirals if influenza wasn’t detected.
“Multiplex testing for respiratory viruses and atypical bacteria is becoming more widespread, with newer-generation platforms having shorter turnaround times, and offers the potential to impact point-of-care decision-making,” she said. “However, these tests are expensive, and more studies are needed to explore whether respiratory pathogen panel testing in the acute care setting has an impact in terms of reduced antibiotic use as well as other outcomes, including ED visits, health-seeking behaviors, and hospitalization.”
For instance, more recent studies around SARS-CoV-2 with newer-generation panels may make a difference, as well as multiplex panels that include numerous viral targets, she said.
“Further RCTs are required to evaluate the impact of influenza/RSV/SARS-CoV-2 panels, as well as respiratory pathogen panel testing in conjunction with antimicrobial and diagnostic stewardship efforts, which have been associated with improved outcomes for other rapid molecular platforms, such as blood culture identification panels,” Rao said.
The study was funded by the Research Institute of the McGill University Health Center. Dr. Schober reported no disclosures, and several study authors reported grants or personal fees from companies outside of this research. Dr. Rao disclosed no relevant relationships.
A version of this article appeared on Medscape.com .
Routine use of rapid respiratory virus testing in the emergency department (ED) appears to show limited benefit among patients with signs and symptoms of acute respiratory infection (ARI), according to a new study.
Rapid viral testing wasn’t associated with reduced antibiotic use, ED length of stay, or rates of ED return visits or hospitalization. However, testing was associated with a small increase in antiviral prescriptions and a small reduction in blood tests and chest x-rays.
“Our interest in studying the benefits of rapid viral testing in emergency departments comes from a commitment to diagnostic stewardship — ensuring that the right tests are administered to the right patients at the right time while also curbing overuse,” said lead author Tilmann Schober, MD, a resident in pediatric infectious disease at McGill University and Montreal Children’s Hospital.
“Following the SARS-CoV-2 pandemic, we have seen a surge in the availability of rapid viral testing, including molecular multiplex panels,” he said. “However, the actual impact of these advancements on patient care in the ED remains uncertain.”
The study was published online on March 4, 2024, in JAMA Internal Medicine).
Rapid Viral Testing
Dr. Schober and colleagues conducted a systematic review and meta-analysis of 11 randomized clinical trials to understand whether rapid testing for respiratory viruses was associated with patient treatment in the ED.
In particular, the research team looked at whether testing in patients with suspected ARI was associated with decreased antibiotic use, ancillary tests, ED length of stay, ED return visits, hospitalization, and increased influenza antiviral treatment.
Among the trials, seven studies included molecular testing, and eight used multiplex panels, including influenza and respiratory syncytial virus (RSV), influenza/RSV/adenovirus/parainfluenza, or a panel of 15 or more respiratory viruses. No study evaluated testing for SARS-CoV-2. The research team reported risk ratios (RRs) and risk difference estimates.
In general, routine rapid viral testing was associated with higher use of influenza antivirals (RR, 1.33) and lower use of chest radiography (RR, 0.88) and blood tests (RR, 0.81). However, the magnitude of these effects was small. For instance, to achieve one additional viral prescription, 70 patients would need to be tested, and to save one x-ray, 30 patients would need to be tested.
“This suggests that, while statistically significant, the practical impact of these secondary outcomes may not justify the extensive effort and resources involved in widespread testing,” Dr. Schober said.
In addition, there was no association between rapid testing and antibiotic use (RR, 0.99), urine testing (RR, 0.95), ED length of stay (0 h), return visits (RR, 0.93), or hospitalization (RR, 1.01).
Notably, there was no association between rapid viral testing and antibiotic use in any prespecified subgroup based on age, test method, publication date, number of viral targets, risk of bias, or industry funding, the authors said. They concluded that rapid virus testing should be reserved for patients for whom the testing will change treatment, such as high-risk patients or those with severe disease.
“It’s crucial to note that our study specifically evaluated the impact of systematic testing of patients with signs and symptoms of acute respiratory infection. Our findings do not advocate against rapid respiratory virus testing in general,” Dr. Schober said. “There is well-established evidence supporting the benefits of viral testing in certain contexts, such as hospitalized patients, to guide infection control practices or in specific high-risk populations.”
Future Research
Additional studies should look at testing among subgroups, particularly those with high-risk conditions, the study authors wrote. In addition, the research team would like to study the implementation of novel diagnostic stewardship programs as compared with well-established antibiotic stewardship programs.
“Acute respiratory tract illnesses represent one of the most common reasons for being evaluated in an acute care setting, especially in pediatrics, and these visits have traditionally resulted in excessive antibiotic prescribing, despite the etiology of the infection mostly being viral,” said Suchitra Rao, MBBS, associate professor of pediatrics at the University of Colorado School of Medicine and associate medical director of infection prevention and control at Children’s Hospital Colorado, Aurora.
Dr. Rao, who wasn’t involved with this study, has surveyed ED providers about respiratory viral testing and changes in clinical decision-making. She and colleagues found that providers most commonly changed clinical decision-making while prescribing an antiviral if influenza was detected or withholding antivirals if influenza wasn’t detected.
“Multiplex testing for respiratory viruses and atypical bacteria is becoming more widespread, with newer-generation platforms having shorter turnaround times, and offers the potential to impact point-of-care decision-making,” she said. “However, these tests are expensive, and more studies are needed to explore whether respiratory pathogen panel testing in the acute care setting has an impact in terms of reduced antibiotic use as well as other outcomes, including ED visits, health-seeking behaviors, and hospitalization.”
For instance, more recent studies around SARS-CoV-2 with newer-generation panels may make a difference, as well as multiplex panels that include numerous viral targets, she said.
“Further RCTs are required to evaluate the impact of influenza/RSV/SARS-CoV-2 panels, as well as respiratory pathogen panel testing in conjunction with antimicrobial and diagnostic stewardship efforts, which have been associated with improved outcomes for other rapid molecular platforms, such as blood culture identification panels,” Rao said.
The study was funded by the Research Institute of the McGill University Health Center. Dr. Schober reported no disclosures, and several study authors reported grants or personal fees from companies outside of this research. Dr. Rao disclosed no relevant relationships.
A version of this article appeared on Medscape.com .
Routine use of rapid respiratory virus testing in the emergency department (ED) appears to show limited benefit among patients with signs and symptoms of acute respiratory infection (ARI), according to a new study.
Rapid viral testing wasn’t associated with reduced antibiotic use, ED length of stay, or rates of ED return visits or hospitalization. However, testing was associated with a small increase in antiviral prescriptions and a small reduction in blood tests and chest x-rays.
“Our interest in studying the benefits of rapid viral testing in emergency departments comes from a commitment to diagnostic stewardship — ensuring that the right tests are administered to the right patients at the right time while also curbing overuse,” said lead author Tilmann Schober, MD, a resident in pediatric infectious disease at McGill University and Montreal Children’s Hospital.
“Following the SARS-CoV-2 pandemic, we have seen a surge in the availability of rapid viral testing, including molecular multiplex panels,” he said. “However, the actual impact of these advancements on patient care in the ED remains uncertain.”
The study was published online on March 4, 2024, in JAMA Internal Medicine).
Rapid Viral Testing
Dr. Schober and colleagues conducted a systematic review and meta-analysis of 11 randomized clinical trials to understand whether rapid testing for respiratory viruses was associated with patient treatment in the ED.
In particular, the research team looked at whether testing in patients with suspected ARI was associated with decreased antibiotic use, ancillary tests, ED length of stay, ED return visits, hospitalization, and increased influenza antiviral treatment.
Among the trials, seven studies included molecular testing, and eight used multiplex panels, including influenza and respiratory syncytial virus (RSV), influenza/RSV/adenovirus/parainfluenza, or a panel of 15 or more respiratory viruses. No study evaluated testing for SARS-CoV-2. The research team reported risk ratios (RRs) and risk difference estimates.
In general, routine rapid viral testing was associated with higher use of influenza antivirals (RR, 1.33) and lower use of chest radiography (RR, 0.88) and blood tests (RR, 0.81). However, the magnitude of these effects was small. For instance, to achieve one additional viral prescription, 70 patients would need to be tested, and to save one x-ray, 30 patients would need to be tested.
“This suggests that, while statistically significant, the practical impact of these secondary outcomes may not justify the extensive effort and resources involved in widespread testing,” Dr. Schober said.
In addition, there was no association between rapid testing and antibiotic use (RR, 0.99), urine testing (RR, 0.95), ED length of stay (0 h), return visits (RR, 0.93), or hospitalization (RR, 1.01).
Notably, there was no association between rapid viral testing and antibiotic use in any prespecified subgroup based on age, test method, publication date, number of viral targets, risk of bias, or industry funding, the authors said. They concluded that rapid virus testing should be reserved for patients for whom the testing will change treatment, such as high-risk patients or those with severe disease.
“It’s crucial to note that our study specifically evaluated the impact of systematic testing of patients with signs and symptoms of acute respiratory infection. Our findings do not advocate against rapid respiratory virus testing in general,” Dr. Schober said. “There is well-established evidence supporting the benefits of viral testing in certain contexts, such as hospitalized patients, to guide infection control practices or in specific high-risk populations.”
Future Research
Additional studies should look at testing among subgroups, particularly those with high-risk conditions, the study authors wrote. In addition, the research team would like to study the implementation of novel diagnostic stewardship programs as compared with well-established antibiotic stewardship programs.
“Acute respiratory tract illnesses represent one of the most common reasons for being evaluated in an acute care setting, especially in pediatrics, and these visits have traditionally resulted in excessive antibiotic prescribing, despite the etiology of the infection mostly being viral,” said Suchitra Rao, MBBS, associate professor of pediatrics at the University of Colorado School of Medicine and associate medical director of infection prevention and control at Children’s Hospital Colorado, Aurora.
Dr. Rao, who wasn’t involved with this study, has surveyed ED providers about respiratory viral testing and changes in clinical decision-making. She and colleagues found that providers most commonly changed clinical decision-making while prescribing an antiviral if influenza was detected or withholding antivirals if influenza wasn’t detected.
“Multiplex testing for respiratory viruses and atypical bacteria is becoming more widespread, with newer-generation platforms having shorter turnaround times, and offers the potential to impact point-of-care decision-making,” she said. “However, these tests are expensive, and more studies are needed to explore whether respiratory pathogen panel testing in the acute care setting has an impact in terms of reduced antibiotic use as well as other outcomes, including ED visits, health-seeking behaviors, and hospitalization.”
For instance, more recent studies around SARS-CoV-2 with newer-generation panels may make a difference, as well as multiplex panels that include numerous viral targets, she said.
“Further RCTs are required to evaluate the impact of influenza/RSV/SARS-CoV-2 panels, as well as respiratory pathogen panel testing in conjunction with antimicrobial and diagnostic stewardship efforts, which have been associated with improved outcomes for other rapid molecular platforms, such as blood culture identification panels,” Rao said.
The study was funded by the Research Institute of the McGill University Health Center. Dr. Schober reported no disclosures, and several study authors reported grants or personal fees from companies outside of this research. Dr. Rao disclosed no relevant relationships.
A version of this article appeared on Medscape.com .