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Epidiolex plus THC lowers seizures in pediatric epilepsy
the component of cannabis that makes people high in larger quantities, researchers reported.
“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.
In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.
CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.
Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.
When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
Combination therapy
For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.
The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).
Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.
The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
Still controversial
Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”
However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.
For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”
University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”
But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”
As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”
No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
the component of cannabis that makes people high in larger quantities, researchers reported.
“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.
In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.
CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.
Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.
When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
Combination therapy
For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.
The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).
Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.
The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
Still controversial
Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”
However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.
For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”
University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”
But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”
As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”
No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
the component of cannabis that makes people high in larger quantities, researchers reported.
“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.
In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.
CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.
Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.
When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
Combination therapy
For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.
The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).
Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.
The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
Still controversial
Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”
However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.
For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”
University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”
But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”
As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”
No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
FROM CNS 2021
‘Baby-wearing’ poses serious injury risks for infants, ED data show
Baby-wearing – carrying a child against your body in a sling, soft carrier, or other device – is associated with benefits like reduced crying and increased breastfeeding, studies have shown.
But this practice also entails risks. Babies can fall out of carriers, or be injured when an adult carrying them falls, for example.
researchers estimated in a study presented at the annual meeting of the American Academy of Pediatrics.
To characterize the epidemiology of these injuries, Samantha J. Rowe, MD, chief resident physician at Walter Reed National Military Medical Center in Bethesda, Md., and colleagues analyzed data from the National Electronic Injury Surveillance System between 2011 and 2020.
They included in their analysis data from patients aged 5 years and younger who sustained an injury associated with a baby-wearing product. Baby harnesses, carriers, slings, framed baby carriers, and soft baby carriers were among the devices included in the study. The researchers used 601 cases to generate national estimates.
An estimated 14,024 patients presented to EDs because of baby-wearing injuries, and 52% of the injuries occurred when a patient fell from the product.
Most injuries (61%) occurred in children aged 5 months and younger; 19.3% of these infants required hospitalization, most often for head injuries.
The investigators found that about 22% of the injuries were associated with a caregiver falling, noted Rachel Y. Moon, MD, who was not involved in the study.
“Carrying a baby changes your center of gravity – and can also obscure your vision of where you’re walking, so adults who use these devices should be cognizant of this,” said Dr. Moon, with the University of Virginia, Charlottesville.
Dr. Rowe often practiced baby-wearing with her daughter, and found that it was beneficial. And studies have demonstrated various benefits of baby-wearing, including improved thermoregulation and glycemic control.
Still, the new analysis illustrates the potential for baby-wearing products “to cause serious injury, especially in infants 5 months and younger,” Dr. Rowe said. “We need to provide more education to caregivers on safe baby-wearing and continue to improve our safety standards for baby-wearing products.”
Study coauthor Patrick T. Reeves, MD, with the Naval Medical Center at San Diego, offered additional guidance in a news release: “Like when buying a new pair of shoes, parents must be educated on the proper sizing, selection, and wear of baby carriers to prevent injury to themselves and their child.”
Parents also need to ensure that the child’s nose and mouth are not obstructed, Dr. Moon
In a recent article discussing the possible benefits of baby-wearing in terms of helping with breastfeeding, Dr. Moon also pointed out further safety considerations: “No matter which carrier is used, for safety reasons, we need to remind parents that the baby should be positioned so that the head is upright and the nose and mouth are not obstructed.”
The researchers and Dr. Moon had no relevant financial disclosures.
Baby-wearing – carrying a child against your body in a sling, soft carrier, or other device – is associated with benefits like reduced crying and increased breastfeeding, studies have shown.
But this practice also entails risks. Babies can fall out of carriers, or be injured when an adult carrying them falls, for example.
researchers estimated in a study presented at the annual meeting of the American Academy of Pediatrics.
To characterize the epidemiology of these injuries, Samantha J. Rowe, MD, chief resident physician at Walter Reed National Military Medical Center in Bethesda, Md., and colleagues analyzed data from the National Electronic Injury Surveillance System between 2011 and 2020.
They included in their analysis data from patients aged 5 years and younger who sustained an injury associated with a baby-wearing product. Baby harnesses, carriers, slings, framed baby carriers, and soft baby carriers were among the devices included in the study. The researchers used 601 cases to generate national estimates.
An estimated 14,024 patients presented to EDs because of baby-wearing injuries, and 52% of the injuries occurred when a patient fell from the product.
Most injuries (61%) occurred in children aged 5 months and younger; 19.3% of these infants required hospitalization, most often for head injuries.
The investigators found that about 22% of the injuries were associated with a caregiver falling, noted Rachel Y. Moon, MD, who was not involved in the study.
“Carrying a baby changes your center of gravity – and can also obscure your vision of where you’re walking, so adults who use these devices should be cognizant of this,” said Dr. Moon, with the University of Virginia, Charlottesville.
Dr. Rowe often practiced baby-wearing with her daughter, and found that it was beneficial. And studies have demonstrated various benefits of baby-wearing, including improved thermoregulation and glycemic control.
Still, the new analysis illustrates the potential for baby-wearing products “to cause serious injury, especially in infants 5 months and younger,” Dr. Rowe said. “We need to provide more education to caregivers on safe baby-wearing and continue to improve our safety standards for baby-wearing products.”
Study coauthor Patrick T. Reeves, MD, with the Naval Medical Center at San Diego, offered additional guidance in a news release: “Like when buying a new pair of shoes, parents must be educated on the proper sizing, selection, and wear of baby carriers to prevent injury to themselves and their child.”
Parents also need to ensure that the child’s nose and mouth are not obstructed, Dr. Moon
In a recent article discussing the possible benefits of baby-wearing in terms of helping with breastfeeding, Dr. Moon also pointed out further safety considerations: “No matter which carrier is used, for safety reasons, we need to remind parents that the baby should be positioned so that the head is upright and the nose and mouth are not obstructed.”
The researchers and Dr. Moon had no relevant financial disclosures.
Baby-wearing – carrying a child against your body in a sling, soft carrier, or other device – is associated with benefits like reduced crying and increased breastfeeding, studies have shown.
But this practice also entails risks. Babies can fall out of carriers, or be injured when an adult carrying them falls, for example.
researchers estimated in a study presented at the annual meeting of the American Academy of Pediatrics.
To characterize the epidemiology of these injuries, Samantha J. Rowe, MD, chief resident physician at Walter Reed National Military Medical Center in Bethesda, Md., and colleagues analyzed data from the National Electronic Injury Surveillance System between 2011 and 2020.
They included in their analysis data from patients aged 5 years and younger who sustained an injury associated with a baby-wearing product. Baby harnesses, carriers, slings, framed baby carriers, and soft baby carriers were among the devices included in the study. The researchers used 601 cases to generate national estimates.
An estimated 14,024 patients presented to EDs because of baby-wearing injuries, and 52% of the injuries occurred when a patient fell from the product.
Most injuries (61%) occurred in children aged 5 months and younger; 19.3% of these infants required hospitalization, most often for head injuries.
The investigators found that about 22% of the injuries were associated with a caregiver falling, noted Rachel Y. Moon, MD, who was not involved in the study.
“Carrying a baby changes your center of gravity – and can also obscure your vision of where you’re walking, so adults who use these devices should be cognizant of this,” said Dr. Moon, with the University of Virginia, Charlottesville.
Dr. Rowe often practiced baby-wearing with her daughter, and found that it was beneficial. And studies have demonstrated various benefits of baby-wearing, including improved thermoregulation and glycemic control.
Still, the new analysis illustrates the potential for baby-wearing products “to cause serious injury, especially in infants 5 months and younger,” Dr. Rowe said. “We need to provide more education to caregivers on safe baby-wearing and continue to improve our safety standards for baby-wearing products.”
Study coauthor Patrick T. Reeves, MD, with the Naval Medical Center at San Diego, offered additional guidance in a news release: “Like when buying a new pair of shoes, parents must be educated on the proper sizing, selection, and wear of baby carriers to prevent injury to themselves and their child.”
Parents also need to ensure that the child’s nose and mouth are not obstructed, Dr. Moon
In a recent article discussing the possible benefits of baby-wearing in terms of helping with breastfeeding, Dr. Moon also pointed out further safety considerations: “No matter which carrier is used, for safety reasons, we need to remind parents that the baby should be positioned so that the head is upright and the nose and mouth are not obstructed.”
The researchers and Dr. Moon had no relevant financial disclosures.
FROM AAP 2021
Is genetic testing valuable in the clinical management of epilepsy?
, new research shows.
Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.
“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.
The findings were presented at the 2021 World Congress of Neurology (WCN).
Test results can be practice-changing
Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.
A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.
The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.
She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.
“Of the physicians who changed treatment, 75% reported there were positive outcomes for the patients,” Dr. McKnight told meeting attendees. “Most common was a reduction or a complete elimination of seizures, and that was reported in 65% of the cases.”
In many cases, the changes resulted in clinical improvements.
“There were 64 individuals who were having daily seizures before the genetic testing,” Dr. McKnight reported via email. “After receiving the genetic diagnosis and modifying their treatment, their physicians reported that 26% of individuals had complete seizure control and 46% of individuals had reduced seizure frequency to either weekly (20%), monthly (20%) or annually (6%).”
The best seizure control after modifying disease management occurred among children. Although the changes were not as dramatic for adults, they trended toward lower seizure frequency.
“It is still pretty significant that adults can receive genetic testing later in life and still have benefit in controlling their seizures,” Dr. McKnight said.
Twenty-three percent of patients showed improvement in behavior, development, academics, or movement issues, while 6% experienced reduced medication side effects.
Dr. McKnight also explored reasons for physicians not making changes to clinical management of patients based on the genetic results. The most common reason was that management was already consistent with the results (47.3%), followed by the results not being informative (26.1%), the results possibly being useful for future treatments in development (19.0%), or other or unknown reasons (7.6%).
Besides direct health and quality of life benefits from better seizure control, Dr. McKnight cited previous economic studies showing lower health care costs.
“It looked like an individual who has good seizure control will incur about 14,000 U.S. dollars a year compared with an individual with pretty poor seizure control, where it can be closer to 23,000 U.S. dollars a year,” Dr. McKnight said. This is mainly attributed to reduced hospitalizations and emergency department visits.
Dr. McKnight noted that currently there is no cost of genetic testing to the patient, the hospital, or insurers. Pharmaceutical companies, she said, sponsor the testing to potentially gather patients for clinical drug trials in development. However, patients remain completely anonymous.
Physicians who wish to have patient samples tested agree that the companies may contact them to ask if any of their patients with positive genetic test results would like to participate in a trial.
Dr. McKnight noted that genetic testing can be considered actionable in the clinic, helping to guide clinical decision-making and potentially leading to better outcomes. Going forward, she suggested performing large case-controlled studies “of individuals with the same genetic etiology ... to really find a true causation or correlation.”
Growing influence of genetic testing
Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.
He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.
“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.
He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.
For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.
Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.
Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.
Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.
“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.
The findings were presented at the 2021 World Congress of Neurology (WCN).
Test results can be practice-changing
Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.
A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.
The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.
She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.
“Of the physicians who changed treatment, 75% reported there were positive outcomes for the patients,” Dr. McKnight told meeting attendees. “Most common was a reduction or a complete elimination of seizures, and that was reported in 65% of the cases.”
In many cases, the changes resulted in clinical improvements.
“There were 64 individuals who were having daily seizures before the genetic testing,” Dr. McKnight reported via email. “After receiving the genetic diagnosis and modifying their treatment, their physicians reported that 26% of individuals had complete seizure control and 46% of individuals had reduced seizure frequency to either weekly (20%), monthly (20%) or annually (6%).”
The best seizure control after modifying disease management occurred among children. Although the changes were not as dramatic for adults, they trended toward lower seizure frequency.
“It is still pretty significant that adults can receive genetic testing later in life and still have benefit in controlling their seizures,” Dr. McKnight said.
Twenty-three percent of patients showed improvement in behavior, development, academics, or movement issues, while 6% experienced reduced medication side effects.
Dr. McKnight also explored reasons for physicians not making changes to clinical management of patients based on the genetic results. The most common reason was that management was already consistent with the results (47.3%), followed by the results not being informative (26.1%), the results possibly being useful for future treatments in development (19.0%), or other or unknown reasons (7.6%).
Besides direct health and quality of life benefits from better seizure control, Dr. McKnight cited previous economic studies showing lower health care costs.
“It looked like an individual who has good seizure control will incur about 14,000 U.S. dollars a year compared with an individual with pretty poor seizure control, where it can be closer to 23,000 U.S. dollars a year,” Dr. McKnight said. This is mainly attributed to reduced hospitalizations and emergency department visits.
Dr. McKnight noted that currently there is no cost of genetic testing to the patient, the hospital, or insurers. Pharmaceutical companies, she said, sponsor the testing to potentially gather patients for clinical drug trials in development. However, patients remain completely anonymous.
Physicians who wish to have patient samples tested agree that the companies may contact them to ask if any of their patients with positive genetic test results would like to participate in a trial.
Dr. McKnight noted that genetic testing can be considered actionable in the clinic, helping to guide clinical decision-making and potentially leading to better outcomes. Going forward, she suggested performing large case-controlled studies “of individuals with the same genetic etiology ... to really find a true causation or correlation.”
Growing influence of genetic testing
Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.
He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.
“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.
He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.
For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.
Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.
Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.
Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.
“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.
The findings were presented at the 2021 World Congress of Neurology (WCN).
Test results can be practice-changing
Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.
A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.
The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.
She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.
“Of the physicians who changed treatment, 75% reported there were positive outcomes for the patients,” Dr. McKnight told meeting attendees. “Most common was a reduction or a complete elimination of seizures, and that was reported in 65% of the cases.”
In many cases, the changes resulted in clinical improvements.
“There were 64 individuals who were having daily seizures before the genetic testing,” Dr. McKnight reported via email. “After receiving the genetic diagnosis and modifying their treatment, their physicians reported that 26% of individuals had complete seizure control and 46% of individuals had reduced seizure frequency to either weekly (20%), monthly (20%) or annually (6%).”
The best seizure control after modifying disease management occurred among children. Although the changes were not as dramatic for adults, they trended toward lower seizure frequency.
“It is still pretty significant that adults can receive genetic testing later in life and still have benefit in controlling their seizures,” Dr. McKnight said.
Twenty-three percent of patients showed improvement in behavior, development, academics, or movement issues, while 6% experienced reduced medication side effects.
Dr. McKnight also explored reasons for physicians not making changes to clinical management of patients based on the genetic results. The most common reason was that management was already consistent with the results (47.3%), followed by the results not being informative (26.1%), the results possibly being useful for future treatments in development (19.0%), or other or unknown reasons (7.6%).
Besides direct health and quality of life benefits from better seizure control, Dr. McKnight cited previous economic studies showing lower health care costs.
“It looked like an individual who has good seizure control will incur about 14,000 U.S. dollars a year compared with an individual with pretty poor seizure control, where it can be closer to 23,000 U.S. dollars a year,” Dr. McKnight said. This is mainly attributed to reduced hospitalizations and emergency department visits.
Dr. McKnight noted that currently there is no cost of genetic testing to the patient, the hospital, or insurers. Pharmaceutical companies, she said, sponsor the testing to potentially gather patients for clinical drug trials in development. However, patients remain completely anonymous.
Physicians who wish to have patient samples tested agree that the companies may contact them to ask if any of their patients with positive genetic test results would like to participate in a trial.
Dr. McKnight noted that genetic testing can be considered actionable in the clinic, helping to guide clinical decision-making and potentially leading to better outcomes. Going forward, she suggested performing large case-controlled studies “of individuals with the same genetic etiology ... to really find a true causation or correlation.”
Growing influence of genetic testing
Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.
He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.
“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.
He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.
For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.
Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.
Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.
Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From WCN 2021
Pediatricians can effectively promote gun safety
When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.
“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.
There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.
In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.
In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.
“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.
However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
Training, guidance, and locks
Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.
For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.
Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.
During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.
The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.
Previous research has shown “a significant increase in safe firearm storage when firearm locks were provided to families in clinic compared to verbal counseling alone,” Dr. Byrne said. “We know that safe firearm storage reduces injuries. Roughly one in three children in the United States lives in a home with a firearm. Individuals with a firearm are at two times the risk of homicide and three to four times the risk of suicide, so it is essential we further study how pediatricians can be most effective when it comes to firearm counseling.”
The difference in lock distribution as a result of the program is a “tremendous increase,” said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine in Houston, who was not involved in the research.
“Locks could go a long way to minimizing the risk,” he said in an interview, adding that nearly half of all teen suicide deaths that occurred over a decade in Houston involved a firearm.
Adding a social-history component
A program to increase firearm screening was also presented at the AAP conference.
After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.
They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.
They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.
From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.
The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.
Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.
The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.
“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”
Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.
Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.
Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.
“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”
Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.
The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.
Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.
“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”
And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.
“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.
“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.
Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”
Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.
“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.
There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.
In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.
In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.
“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.
However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
Training, guidance, and locks
Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.
For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.
Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.
During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.
The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.
Previous research has shown “a significant increase in safe firearm storage when firearm locks were provided to families in clinic compared to verbal counseling alone,” Dr. Byrne said. “We know that safe firearm storage reduces injuries. Roughly one in three children in the United States lives in a home with a firearm. Individuals with a firearm are at two times the risk of homicide and three to four times the risk of suicide, so it is essential we further study how pediatricians can be most effective when it comes to firearm counseling.”
The difference in lock distribution as a result of the program is a “tremendous increase,” said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine in Houston, who was not involved in the research.
“Locks could go a long way to minimizing the risk,” he said in an interview, adding that nearly half of all teen suicide deaths that occurred over a decade in Houston involved a firearm.
Adding a social-history component
A program to increase firearm screening was also presented at the AAP conference.
After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.
They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.
They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.
From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.
The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.
Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.
The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.
“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”
Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.
Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.
Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.
“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”
Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.
The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.
Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.
“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”
And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.
“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.
“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.
Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”
Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.
“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.
There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.
In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.
In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.
“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.
However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
Training, guidance, and locks
Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.
For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.
Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.
During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.
The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.
Previous research has shown “a significant increase in safe firearm storage when firearm locks were provided to families in clinic compared to verbal counseling alone,” Dr. Byrne said. “We know that safe firearm storage reduces injuries. Roughly one in three children in the United States lives in a home with a firearm. Individuals with a firearm are at two times the risk of homicide and three to four times the risk of suicide, so it is essential we further study how pediatricians can be most effective when it comes to firearm counseling.”
The difference in lock distribution as a result of the program is a “tremendous increase,” said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine in Houston, who was not involved in the research.
“Locks could go a long way to minimizing the risk,” he said in an interview, adding that nearly half of all teen suicide deaths that occurred over a decade in Houston involved a firearm.
Adding a social-history component
A program to increase firearm screening was also presented at the AAP conference.
After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.
They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.
They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.
From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.
The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.
Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.
The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.
“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”
Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.
Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.
Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.
“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”
Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.
The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.
Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.
“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”
And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.
“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.
“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.
Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”
Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAP 2021
You’ve been uneasy about the mother’s boyfriend: This may be why
The first patient of the afternoon is a 4-month-old in for his health maintenance visit. You’ve known his 20-year-old mother since she was a toddler. This infant has a 2-year-old sister. Also in the exam room is a young man you don’t recognize whom the mother introduces as Jason, her new boyfriend. He never makes eye contact and despite your best efforts you can’t get him to engage.
At the child’s next visit you are relieved to see the 6-month-old is alive and well and learn that your former patient and her two children have moved back in with her parents and Jason is no longer in the picture.
You don’t have to have been doing pediatrics very long to have learned that a “family” that includes an infant and a young adult male who is probably not the father is an environment in which the infant’s health and well-being is at significant risk. It is a situation in which child abuse even to the point of infanticide should be waving a red flag in your face.
Infanticide occurs in many animal species including our own. As abhorrent we may find the act, it occurs often enough to be, if not normal, at least not unexpected in certain circumstances. Theories abound as to what advantage the act of infanticide might convey to the success of a species. However, little if anything is known about any possible mechanisms that would allow it to occur.
Recently, a professor of molecular and cellular biology at Harvard University discovered a specific set of neurons in the mouse brain that controls aggressive behavior toward infants (Biological triggers for infant abuse, by Juan Siliezar, The Harvard Gazette, Sept 27, 2021). This same set of neurons also appears to trigger avoidance and neglect behaviors as well.
Research in other animal species has found that these antiparental behaviors occur in both virgins and sexually mature males who are strangers to the group. Interestingly, the behaviors switch off once individuals have their own offspring or have had the opportunity to familiarize themselves with infants. Not surprisingly, other studies have found that in some species environmental stress such as food shortage or threats of predation have triggered females to attack or ignore their offspring.
I think it is safe to assume a similar collection of neurons controlling aggressive behavior also exists in humans. One can imagine some well-read defense attorney dredging up this study and claiming that because his client had not yet fathered a child of his own that it was his nervous system’s normal response that made him toss his girlfriend’s baby against the wall.
The lead author of the study intends to study this collection of neurons in more depth to discover more about the process. It is conceivable that with more information her initial findings may help in the development of treatment and specific prevention strategies. Until that happens, we must rely on our intuition and keep our antennae tuned and alert for high-risk scenarios like the one I described at the opening of this letter.
We are left with leaning heavily on our community social work networks to keep close tabs on these high-risk families, offering both financial and emotional support. Parenting classes may be helpful, but some of this research leads me to suspect that immersing these young parents-to-be in hands-on child care situations might provide the best protection we can offer.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
The first patient of the afternoon is a 4-month-old in for his health maintenance visit. You’ve known his 20-year-old mother since she was a toddler. This infant has a 2-year-old sister. Also in the exam room is a young man you don’t recognize whom the mother introduces as Jason, her new boyfriend. He never makes eye contact and despite your best efforts you can’t get him to engage.
At the child’s next visit you are relieved to see the 6-month-old is alive and well and learn that your former patient and her two children have moved back in with her parents and Jason is no longer in the picture.
You don’t have to have been doing pediatrics very long to have learned that a “family” that includes an infant and a young adult male who is probably not the father is an environment in which the infant’s health and well-being is at significant risk. It is a situation in which child abuse even to the point of infanticide should be waving a red flag in your face.
Infanticide occurs in many animal species including our own. As abhorrent we may find the act, it occurs often enough to be, if not normal, at least not unexpected in certain circumstances. Theories abound as to what advantage the act of infanticide might convey to the success of a species. However, little if anything is known about any possible mechanisms that would allow it to occur.
Recently, a professor of molecular and cellular biology at Harvard University discovered a specific set of neurons in the mouse brain that controls aggressive behavior toward infants (Biological triggers for infant abuse, by Juan Siliezar, The Harvard Gazette, Sept 27, 2021). This same set of neurons also appears to trigger avoidance and neglect behaviors as well.
Research in other animal species has found that these antiparental behaviors occur in both virgins and sexually mature males who are strangers to the group. Interestingly, the behaviors switch off once individuals have their own offspring or have had the opportunity to familiarize themselves with infants. Not surprisingly, other studies have found that in some species environmental stress such as food shortage or threats of predation have triggered females to attack or ignore their offspring.
I think it is safe to assume a similar collection of neurons controlling aggressive behavior also exists in humans. One can imagine some well-read defense attorney dredging up this study and claiming that because his client had not yet fathered a child of his own that it was his nervous system’s normal response that made him toss his girlfriend’s baby against the wall.
The lead author of the study intends to study this collection of neurons in more depth to discover more about the process. It is conceivable that with more information her initial findings may help in the development of treatment and specific prevention strategies. Until that happens, we must rely on our intuition and keep our antennae tuned and alert for high-risk scenarios like the one I described at the opening of this letter.
We are left with leaning heavily on our community social work networks to keep close tabs on these high-risk families, offering both financial and emotional support. Parenting classes may be helpful, but some of this research leads me to suspect that immersing these young parents-to-be in hands-on child care situations might provide the best protection we can offer.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
The first patient of the afternoon is a 4-month-old in for his health maintenance visit. You’ve known his 20-year-old mother since she was a toddler. This infant has a 2-year-old sister. Also in the exam room is a young man you don’t recognize whom the mother introduces as Jason, her new boyfriend. He never makes eye contact and despite your best efforts you can’t get him to engage.
At the child’s next visit you are relieved to see the 6-month-old is alive and well and learn that your former patient and her two children have moved back in with her parents and Jason is no longer in the picture.
You don’t have to have been doing pediatrics very long to have learned that a “family” that includes an infant and a young adult male who is probably not the father is an environment in which the infant’s health and well-being is at significant risk. It is a situation in which child abuse even to the point of infanticide should be waving a red flag in your face.
Infanticide occurs in many animal species including our own. As abhorrent we may find the act, it occurs often enough to be, if not normal, at least not unexpected in certain circumstances. Theories abound as to what advantage the act of infanticide might convey to the success of a species. However, little if anything is known about any possible mechanisms that would allow it to occur.
Recently, a professor of molecular and cellular biology at Harvard University discovered a specific set of neurons in the mouse brain that controls aggressive behavior toward infants (Biological triggers for infant abuse, by Juan Siliezar, The Harvard Gazette, Sept 27, 2021). This same set of neurons also appears to trigger avoidance and neglect behaviors as well.
Research in other animal species has found that these antiparental behaviors occur in both virgins and sexually mature males who are strangers to the group. Interestingly, the behaviors switch off once individuals have their own offspring or have had the opportunity to familiarize themselves with infants. Not surprisingly, other studies have found that in some species environmental stress such as food shortage or threats of predation have triggered females to attack or ignore their offspring.
I think it is safe to assume a similar collection of neurons controlling aggressive behavior also exists in humans. One can imagine some well-read defense attorney dredging up this study and claiming that because his client had not yet fathered a child of his own that it was his nervous system’s normal response that made him toss his girlfriend’s baby against the wall.
The lead author of the study intends to study this collection of neurons in more depth to discover more about the process. It is conceivable that with more information her initial findings may help in the development of treatment and specific prevention strategies. Until that happens, we must rely on our intuition and keep our antennae tuned and alert for high-risk scenarios like the one I described at the opening of this letter.
We are left with leaning heavily on our community social work networks to keep close tabs on these high-risk families, offering both financial and emotional support. Parenting classes may be helpful, but some of this research leads me to suspect that immersing these young parents-to-be in hands-on child care situations might provide the best protection we can offer.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Synthetic chemical in consumer products linked to early death, study says
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Children and COVID-19: U.S. adds latest million cases in record time
The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.
The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.
New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.
Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.
The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.
That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”
The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.
The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.
New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.
Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.
The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.
That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”
The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.
The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.
New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.
Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.
The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.
That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”
Acyclovir-Resistant Cutaneous Herpes Simplex Virus in DOCK8 Deficiency
Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. 1 Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). 1 In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. 2 Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. 1 Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV.
Case Report
A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.
During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.
After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion. The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.
Comment
Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.3 Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.4
Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.5 Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.6 However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.
Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.6 Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.
Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.6 For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.
Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.6 Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.12 Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).7 There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.7-9
The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.
Conclusion
DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.
- Chu EY, Freeman AF, Jing H, et al. Cutaneous manifestations of DOCK8 deficiency syndrome. Arch Dermatol. 2012;148:79-84. doi:10.1001/archdermatol.2011.262
- Aydin SE, Kilic SS, Aytekin C, et al. DOCK8 deficiency: clinical and immunological phenotype and treatment options—a review of 136 patients. J Clin Immunol. 2015;35:189-198. doi:10.1007/s10875-014-0126-0
- Kearney CJ, Randall KL, Oliaro J. DOCK8 regulates signal transduction events to control immunity. Cell Mol Immunol. 2017;14:406-411. doi:10.1038/cmi.2017.9
- Zhang Q, Dove CG, Hor JL, et al. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med. 2014;211:2549-2566. doi:10.1084/jem.20141307
- Engelhardt KR, Gertz EM, Keles S, et al. The extended clinical phenotype of 64 patients with DOCK8 deficiency. J Allergy Clin Immunol. 2015;136:402-412. doi:10.1016/j.jaci.2014.12.1945
- Chilukuri S, Rosen T. Management of acyclovir-resistant herpes simplex virus. Dermatol Clin. 2003;21:311-320. doi:10.1016/S0733-8635(02)00093-1
- Keles S, Jabara HH, Reisli I, et al. Plasmacytoid dendritic cell depletion in DOCK8 deficiency: rescue of severe herpetic infections with interferon alpha-2b therapy. J Allergy Clin Immunol. 2014;133:1753-1755.e3. doi:10.1016/j.jaci.2014.03.032
- Papan C, Hagl B, Heinz V, et al Beneficial IFN-α treatment of tumorous herpes simplex blepharoconjunctivitis in dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol. 2014;133:1456-1458. doi:10.1016/j.jaci.2014.02.008
- Metin A, Kanik-Yuksek S, Ozkaya-Parlakay A, et al. Giant herpes labialis in a child with DOCK8-deficient hyper-IgE syndrome. Pediatr Neonatol. 2016;57:79-80. doi:10.1016/j.pedneo.2015.04.011
- Zhang Q, Davis JC, Lamborn IT, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009;361:2046-2055. doi:10.1056/NEJMoa0905506
- Lei JY, Wang Y, Jaffe ES, et al. Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma. Am J Dermatopathol. 2000;22:524-529. doi:10.1097/00000372-200012000-00008
- Castelo-Soccio L, Bernardin R, Stern J, et al. Successful treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir. Arch Dermatol. 2010;146:124-126. doi:10.1001/archdermatol.2009.363
- Shah NN, Freeman AF, Hickstein DD. Addendum to: haploidentical related donor hematopoietic stem cell transplantation for DOCK8 deficiency using post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2019;25:E65-E67. doi:10.1016/j.bbmt.2018.11.014
- Freeman AF, Yazigi N, Shah NN, et al. Tandem orthotopic living donor liver transplantation followed by same donor haploidentical hematopoietic stem cell transplantation for DOCK8 deficiency. Transplantation. 2019;103:2144-2149. doi:10.1097/TP.0000000000002649
- Casto AM, Stout SC, Selvarangan R, et al. Evaluation of genotypic antiviral resistance testing as an alternative to phenotypic testing in a patient with DOCK8 deficiency and severe HSV-1 disease. J Infect Dis. 2020;221:2035-2042. doi:10.1093/infdis/jiaa020
Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. 1 Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). 1 In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. 2 Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. 1 Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV.
Case Report
A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.
During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.
After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion. The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.
Comment
Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.3 Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.4
Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.5 Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.6 However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.
Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.6 Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.
Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.6 For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.
Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.6 Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.12 Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).7 There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.7-9
The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.
Conclusion
DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.
Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. 1 Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). 1 In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. 2 Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. 1 Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV.
Case Report
A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.
During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.
After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion. The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.
Comment
Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.3 Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.4
Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.5 Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.6 However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.
Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.6 Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.
Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.6 For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.
Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.6 Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.12 Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).7 There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.7-9
The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.
Conclusion
DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.
- Chu EY, Freeman AF, Jing H, et al. Cutaneous manifestations of DOCK8 deficiency syndrome. Arch Dermatol. 2012;148:79-84. doi:10.1001/archdermatol.2011.262
- Aydin SE, Kilic SS, Aytekin C, et al. DOCK8 deficiency: clinical and immunological phenotype and treatment options—a review of 136 patients. J Clin Immunol. 2015;35:189-198. doi:10.1007/s10875-014-0126-0
- Kearney CJ, Randall KL, Oliaro J. DOCK8 regulates signal transduction events to control immunity. Cell Mol Immunol. 2017;14:406-411. doi:10.1038/cmi.2017.9
- Zhang Q, Dove CG, Hor JL, et al. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med. 2014;211:2549-2566. doi:10.1084/jem.20141307
- Engelhardt KR, Gertz EM, Keles S, et al. The extended clinical phenotype of 64 patients with DOCK8 deficiency. J Allergy Clin Immunol. 2015;136:402-412. doi:10.1016/j.jaci.2014.12.1945
- Chilukuri S, Rosen T. Management of acyclovir-resistant herpes simplex virus. Dermatol Clin. 2003;21:311-320. doi:10.1016/S0733-8635(02)00093-1
- Keles S, Jabara HH, Reisli I, et al. Plasmacytoid dendritic cell depletion in DOCK8 deficiency: rescue of severe herpetic infections with interferon alpha-2b therapy. J Allergy Clin Immunol. 2014;133:1753-1755.e3. doi:10.1016/j.jaci.2014.03.032
- Papan C, Hagl B, Heinz V, et al Beneficial IFN-α treatment of tumorous herpes simplex blepharoconjunctivitis in dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol. 2014;133:1456-1458. doi:10.1016/j.jaci.2014.02.008
- Metin A, Kanik-Yuksek S, Ozkaya-Parlakay A, et al. Giant herpes labialis in a child with DOCK8-deficient hyper-IgE syndrome. Pediatr Neonatol. 2016;57:79-80. doi:10.1016/j.pedneo.2015.04.011
- Zhang Q, Davis JC, Lamborn IT, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009;361:2046-2055. doi:10.1056/NEJMoa0905506
- Lei JY, Wang Y, Jaffe ES, et al. Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma. Am J Dermatopathol. 2000;22:524-529. doi:10.1097/00000372-200012000-00008
- Castelo-Soccio L, Bernardin R, Stern J, et al. Successful treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir. Arch Dermatol. 2010;146:124-126. doi:10.1001/archdermatol.2009.363
- Shah NN, Freeman AF, Hickstein DD. Addendum to: haploidentical related donor hematopoietic stem cell transplantation for DOCK8 deficiency using post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2019;25:E65-E67. doi:10.1016/j.bbmt.2018.11.014
- Freeman AF, Yazigi N, Shah NN, et al. Tandem orthotopic living donor liver transplantation followed by same donor haploidentical hematopoietic stem cell transplantation for DOCK8 deficiency. Transplantation. 2019;103:2144-2149. doi:10.1097/TP.0000000000002649
- Casto AM, Stout SC, Selvarangan R, et al. Evaluation of genotypic antiviral resistance testing as an alternative to phenotypic testing in a patient with DOCK8 deficiency and severe HSV-1 disease. J Infect Dis. 2020;221:2035-2042. doi:10.1093/infdis/jiaa020
- Chu EY, Freeman AF, Jing H, et al. Cutaneous manifestations of DOCK8 deficiency syndrome. Arch Dermatol. 2012;148:79-84. doi:10.1001/archdermatol.2011.262
- Aydin SE, Kilic SS, Aytekin C, et al. DOCK8 deficiency: clinical and immunological phenotype and treatment options—a review of 136 patients. J Clin Immunol. 2015;35:189-198. doi:10.1007/s10875-014-0126-0
- Kearney CJ, Randall KL, Oliaro J. DOCK8 regulates signal transduction events to control immunity. Cell Mol Immunol. 2017;14:406-411. doi:10.1038/cmi.2017.9
- Zhang Q, Dove CG, Hor JL, et al. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med. 2014;211:2549-2566. doi:10.1084/jem.20141307
- Engelhardt KR, Gertz EM, Keles S, et al. The extended clinical phenotype of 64 patients with DOCK8 deficiency. J Allergy Clin Immunol. 2015;136:402-412. doi:10.1016/j.jaci.2014.12.1945
- Chilukuri S, Rosen T. Management of acyclovir-resistant herpes simplex virus. Dermatol Clin. 2003;21:311-320. doi:10.1016/S0733-8635(02)00093-1
- Keles S, Jabara HH, Reisli I, et al. Plasmacytoid dendritic cell depletion in DOCK8 deficiency: rescue of severe herpetic infections with interferon alpha-2b therapy. J Allergy Clin Immunol. 2014;133:1753-1755.e3. doi:10.1016/j.jaci.2014.03.032
- Papan C, Hagl B, Heinz V, et al Beneficial IFN-α treatment of tumorous herpes simplex blepharoconjunctivitis in dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol. 2014;133:1456-1458. doi:10.1016/j.jaci.2014.02.008
- Metin A, Kanik-Yuksek S, Ozkaya-Parlakay A, et al. Giant herpes labialis in a child with DOCK8-deficient hyper-IgE syndrome. Pediatr Neonatol. 2016;57:79-80. doi:10.1016/j.pedneo.2015.04.011
- Zhang Q, Davis JC, Lamborn IT, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009;361:2046-2055. doi:10.1056/NEJMoa0905506
- Lei JY, Wang Y, Jaffe ES, et al. Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma. Am J Dermatopathol. 2000;22:524-529. doi:10.1097/00000372-200012000-00008
- Castelo-Soccio L, Bernardin R, Stern J, et al. Successful treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir. Arch Dermatol. 2010;146:124-126. doi:10.1001/archdermatol.2009.363
- Shah NN, Freeman AF, Hickstein DD. Addendum to: haploidentical related donor hematopoietic stem cell transplantation for DOCK8 deficiency using post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2019;25:E65-E67. doi:10.1016/j.bbmt.2018.11.014
- Freeman AF, Yazigi N, Shah NN, et al. Tandem orthotopic living donor liver transplantation followed by same donor haploidentical hematopoietic stem cell transplantation for DOCK8 deficiency. Transplantation. 2019;103:2144-2149. doi:10.1097/TP.0000000000002649
- Casto AM, Stout SC, Selvarangan R, et al. Evaluation of genotypic antiviral resistance testing as an alternative to phenotypic testing in a patient with DOCK8 deficiency and severe HSV-1 disease. J Infect Dis. 2020;221:2035-2042. doi:10.1093/infdis/jiaa020
Practice Points
- Patients with dedicator of cytokinesis 8 ( DOCK 8 ) deficiency are susceptible to development of severe recalcitrant viral cutaneous infections, including herpes simplex virus (HSV).
- Dermatologists should be aware that prophylactic acyclovir may not be sufficient for HSV suppression in the setting of severe immunodeficiency.
- Acyclovir-resistant cutaneous HSV lesions require escalation of therapy, which may include addition of foscarnet, cidofovir, or subcutaneous pegylated interferon alfa-2b to the therapeutic regimen.
- Viral culture should be performed on suspicious lesions in DOCK 8 -deficient patients despite acyclovir prophylaxis, and the threshold for HSV resistance testing should be low.
Bystander actions can reduce children’s risk of drowning
The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.
“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.
“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.
The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.
“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”
Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.
In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.
They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.
Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).
The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).
However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.
The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.
“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.
Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.
“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”
The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.
The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.
“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.
Dr. Shenoi echoed this sentiment.
“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”
The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.
Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.
A version of this article first appeared on Medscape.com.
The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.
“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.
“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.
The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.
“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”
Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.
In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.
They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.
Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).
The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).
However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.
The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.
“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.
Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.
“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”
The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.
The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.
“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.
Dr. Shenoi echoed this sentiment.
“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”
The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.
Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.
A version of this article first appeared on Medscape.com.
The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.
“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.
“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.
The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.
“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”
Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.
In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.
They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.
Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).
The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).
However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.
The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.
“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.
Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.
“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”
The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.
The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.
“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.
Dr. Shenoi echoed this sentiment.
“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”
The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.
Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.
A version of this article first appeared on Medscape.com.
Effect of COVID-19 pandemic on respiratory infectious diseases in primary care practice
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.