Pediatric News

Owning an outdoor cat as a child is associated with an increased risk of psychotic experiences in adulthood – but only in males, new research suggests.

Investigators found male children who owned cats that went outside had a small, but significantly increased, risk of psychotic experiences in adulthood, compared with their counterparts who had no cat during childhood or who had an indoor cat.

Courtesy McGill University

The suspected culprit is not the cat itself but rather exposure to Toxoplasma gondii, a common parasite carried by rodents and sometimes found in cat feces. The study adds to a growing evidence showing exposure to T. gondii may be a risk factor for schizophrenia and other psychotic disorders.

“These are small pieces of evidence but it’s interesting to consider that there might be combinations of risk factors at play,” lead author Vincent Paquin, MD, psychiatry resident at McGill University, Montreal, said in an interview.

“And even if the magnitude of the risk is small at the individual level,” he added, “cats and Toxoplasma gondii are so present in our society that if we add up all these small potential effects then it becomes a potential public health question.”

The study was published online Jan. 30, 2022, in the Journal of Psychiatric Research.
 

Inconsistent evidence

T. gondii infects about 30% of the human population and is usually transmitted by cats. Most infections are asymptomatic, but T. gondii can cause toxoplasmosis in humans, which has been linked to increased risk of schizophrenia, suicide attempts, and more recently, mild cognitive impairment.

Although some studies show an association between cat ownership and increased risk of mental illness, the research findings have been inconsistent.

“The evidence has been mixed about the association between cat ownership and psychosis expression, so our approach was to consider whether specific factors or combinations of factors could explain this mixed evidence,” Dr. Paquin said.

For the study, 2206 individuals aged 18-40 years completed the Community Assessment of Psychic Experiences (CAPE-42) and a questionnaire to gather information about cat ownership at any time between birth and age 13 and if the cats lived exclusively indoors (nonhunting) or if they were allowed outside (rodent hunting).

Participants were also asked about the number of residential moves between birth and age 15, date and place of birth, lifetime history of head trauma, and tobacco smoking history.

Rodent-hunting cat ownership was associated with higher risk of psychosis in male participants, compared with owning no cat or a nonhunting cat. When the investigators added head trauma and residential moves to rodent-hunting cat ownership, psychosis risk was elevated in both men and women.

Independent of cat ownership, younger age, moving more than three times as a child, a history of head trauma, and being a smoker were all associated with higher psychosis risk.

Courtesy McGill University

The study wasn’t designed to explore potential biological mechanisms to explain the sex differences in psychosis risk seen among rodent-hunting cat owners, but “one possible explanation based on the animal model literature is that the neurobiological effects of parasitic exposure may be greater with male sex,” senior author Suzanne King, PhD, professor of psychiatry at McGill, said in an interview.

The new study is part of a larger, long-term project called EnviroGen, led by Dr. King, examining the environmental and genetic risk factors for schizophrenia.
 

Need for replication

Commenting on the findings, E. Fuller Torrey, MD, who was among the first researchers to identify a link between cat ownership, T. gondii infection, and schizophrenia, said the study is “an interesting addition to the studies of cat ownership in childhood as a risk factor for psychosis.”

Of the approximately 10 published studies on the topic, about half suggest a link between cat ownership and psychosis later in life, said Dr. Torrey, associate director for research at the Stanley Medical Research Institute in Rockville, Md.

“The Canadian study is interesting in that it is the first study that separates exposure to permanently indoor cats from cats that are allowed to go outdoors, and the results were positive only for outdoor cats,” Dr. Torrey said.

The study has limitations, Dr. Torrey added, including its retrospective design and the use of a self-report questionnaire to assess psychotic experiences in adulthood.

Also commenting on findings, James Kirkbride, PhD, professor of psychiatric and social epidemiology, University College London, noted the same limitations.

Dr. Kirkbride is the lead author of a 2017 study that showed no link between cat ownership and serious mental illness that included nearly 5,000 people born in 1991 or 1992 and followed until age 18. In this study, there was no link between psychosis and cat ownership during pregnancy or at ages 4 or 10 years.

“Researchers have long been fascinated with the idea that cat ownership may affect mental health. This paper may have them chasing their own tail,” Dr. Kirkbride said.

“Evidence of any association is limited to certain subgroups without a strong theoretical basis for why this may be the case,” he added. “The retrospective and cross-sectional nature of the survey also raise the possibility that the results are impacted by differential recall bias, as well as the broader issues of chance and unobserved confounding.”

Dr. King noted that recall bias is a limitation the researchers highlighted in their study, but “considering the exposures are relatively objective and factual, we do not believe the potential for recall bias is substantial.”

“Nonetheless, we strongly believe that replication of our results in prospective, population-representative cohorts will be crucial to making firmer conclusions,” he added.

The study was funded by grants from the Quebec Health Research Fund. The study authors and Dr. Kirkbride disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Owning an outdoor cat as a child is associated with an increased risk of psychotic experiences in adulthood – but only in males, new research suggests.

Investigators found male children who owned cats that went outside had a small, but significantly increased, risk of psychotic experiences in adulthood, compared with their counterparts who had no cat during childhood or who had an indoor cat.

Courtesy McGill University

The suspected culprit is not the cat itself but rather exposure to Toxoplasma gondii, a common parasite carried by rodents and sometimes found in cat feces. The study adds to a growing evidence showing exposure to T. gondii may be a risk factor for schizophrenia and other psychotic disorders.

“These are small pieces of evidence but it’s interesting to consider that there might be combinations of risk factors at play,” lead author Vincent Paquin, MD, psychiatry resident at McGill University, Montreal, said in an interview.

“And even if the magnitude of the risk is small at the individual level,” he added, “cats and Toxoplasma gondii are so present in our society that if we add up all these small potential effects then it becomes a potential public health question.”

The study was published online Jan. 30, 2022, in the Journal of Psychiatric Research.
 

Inconsistent evidence

T. gondii infects about 30% of the human population and is usually transmitted by cats. Most infections are asymptomatic, but T. gondii can cause toxoplasmosis in humans, which has been linked to increased risk of schizophrenia, suicide attempts, and more recently, mild cognitive impairment.

Although some studies show an association between cat ownership and increased risk of mental illness, the research findings have been inconsistent.

“The evidence has been mixed about the association between cat ownership and psychosis expression, so our approach was to consider whether specific factors or combinations of factors could explain this mixed evidence,” Dr. Paquin said.

For the study, 2206 individuals aged 18-40 years completed the Community Assessment of Psychic Experiences (CAPE-42) and a questionnaire to gather information about cat ownership at any time between birth and age 13 and if the cats lived exclusively indoors (nonhunting) or if they were allowed outside (rodent hunting).

Participants were also asked about the number of residential moves between birth and age 15, date and place of birth, lifetime history of head trauma, and tobacco smoking history.

Rodent-hunting cat ownership was associated with higher risk of psychosis in male participants, compared with owning no cat or a nonhunting cat. When the investigators added head trauma and residential moves to rodent-hunting cat ownership, psychosis risk was elevated in both men and women.

Independent of cat ownership, younger age, moving more than three times as a child, a history of head trauma, and being a smoker were all associated with higher psychosis risk.

Courtesy McGill University

The study wasn’t designed to explore potential biological mechanisms to explain the sex differences in psychosis risk seen among rodent-hunting cat owners, but “one possible explanation based on the animal model literature is that the neurobiological effects of parasitic exposure may be greater with male sex,” senior author Suzanne King, PhD, professor of psychiatry at McGill, said in an interview.

The new study is part of a larger, long-term project called EnviroGen, led by Dr. King, examining the environmental and genetic risk factors for schizophrenia.
 

Need for replication

Commenting on the findings, E. Fuller Torrey, MD, who was among the first researchers to identify a link between cat ownership, T. gondii infection, and schizophrenia, said the study is “an interesting addition to the studies of cat ownership in childhood as a risk factor for psychosis.”

Of the approximately 10 published studies on the topic, about half suggest a link between cat ownership and psychosis later in life, said Dr. Torrey, associate director for research at the Stanley Medical Research Institute in Rockville, Md.

“The Canadian study is interesting in that it is the first study that separates exposure to permanently indoor cats from cats that are allowed to go outdoors, and the results were positive only for outdoor cats,” Dr. Torrey said.

The study has limitations, Dr. Torrey added, including its retrospective design and the use of a self-report questionnaire to assess psychotic experiences in adulthood.

Also commenting on findings, James Kirkbride, PhD, professor of psychiatric and social epidemiology, University College London, noted the same limitations.

Dr. Kirkbride is the lead author of a 2017 study that showed no link between cat ownership and serious mental illness that included nearly 5,000 people born in 1991 or 1992 and followed until age 18. In this study, there was no link between psychosis and cat ownership during pregnancy or at ages 4 or 10 years.

“Researchers have long been fascinated with the idea that cat ownership may affect mental health. This paper may have them chasing their own tail,” Dr. Kirkbride said.

“Evidence of any association is limited to certain subgroups without a strong theoretical basis for why this may be the case,” he added. “The retrospective and cross-sectional nature of the survey also raise the possibility that the results are impacted by differential recall bias, as well as the broader issues of chance and unobserved confounding.”

Dr. King noted that recall bias is a limitation the researchers highlighted in their study, but “considering the exposures are relatively objective and factual, we do not believe the potential for recall bias is substantial.”

“Nonetheless, we strongly believe that replication of our results in prospective, population-representative cohorts will be crucial to making firmer conclusions,” he added.

The study was funded by grants from the Quebec Health Research Fund. The study authors and Dr. Kirkbride disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Owning an outdoor cat as a child is associated with an increased risk of psychotic experiences in adulthood – but only in males, new research suggests.

Investigators found male children who owned cats that went outside had a small, but significantly increased, risk of psychotic experiences in adulthood, compared with their counterparts who had no cat during childhood or who had an indoor cat.

Courtesy McGill University

The suspected culprit is not the cat itself but rather exposure to Toxoplasma gondii, a common parasite carried by rodents and sometimes found in cat feces. The study adds to a growing evidence showing exposure to T. gondii may be a risk factor for schizophrenia and other psychotic disorders.

“These are small pieces of evidence but it’s interesting to consider that there might be combinations of risk factors at play,” lead author Vincent Paquin, MD, psychiatry resident at McGill University, Montreal, said in an interview.

“And even if the magnitude of the risk is small at the individual level,” he added, “cats and Toxoplasma gondii are so present in our society that if we add up all these small potential effects then it becomes a potential public health question.”

The study was published online Jan. 30, 2022, in the Journal of Psychiatric Research.
 

Inconsistent evidence

T. gondii infects about 30% of the human population and is usually transmitted by cats. Most infections are asymptomatic, but T. gondii can cause toxoplasmosis in humans, which has been linked to increased risk of schizophrenia, suicide attempts, and more recently, mild cognitive impairment.

Although some studies show an association between cat ownership and increased risk of mental illness, the research findings have been inconsistent.

“The evidence has been mixed about the association between cat ownership and psychosis expression, so our approach was to consider whether specific factors or combinations of factors could explain this mixed evidence,” Dr. Paquin said.

For the study, 2206 individuals aged 18-40 years completed the Community Assessment of Psychic Experiences (CAPE-42) and a questionnaire to gather information about cat ownership at any time between birth and age 13 and if the cats lived exclusively indoors (nonhunting) or if they were allowed outside (rodent hunting).

Participants were also asked about the number of residential moves between birth and age 15, date and place of birth, lifetime history of head trauma, and tobacco smoking history.

Rodent-hunting cat ownership was associated with higher risk of psychosis in male participants, compared with owning no cat or a nonhunting cat. When the investigators added head trauma and residential moves to rodent-hunting cat ownership, psychosis risk was elevated in both men and women.

Independent of cat ownership, younger age, moving more than three times as a child, a history of head trauma, and being a smoker were all associated with higher psychosis risk.

Courtesy McGill University

The study wasn’t designed to explore potential biological mechanisms to explain the sex differences in psychosis risk seen among rodent-hunting cat owners, but “one possible explanation based on the animal model literature is that the neurobiological effects of parasitic exposure may be greater with male sex,” senior author Suzanne King, PhD, professor of psychiatry at McGill, said in an interview.

The new study is part of a larger, long-term project called EnviroGen, led by Dr. King, examining the environmental and genetic risk factors for schizophrenia.
 

Need for replication

Commenting on the findings, E. Fuller Torrey, MD, who was among the first researchers to identify a link between cat ownership, T. gondii infection, and schizophrenia, said the study is “an interesting addition to the studies of cat ownership in childhood as a risk factor for psychosis.”

Of the approximately 10 published studies on the topic, about half suggest a link between cat ownership and psychosis later in life, said Dr. Torrey, associate director for research at the Stanley Medical Research Institute in Rockville, Md.

“The Canadian study is interesting in that it is the first study that separates exposure to permanently indoor cats from cats that are allowed to go outdoors, and the results were positive only for outdoor cats,” Dr. Torrey said.

The study has limitations, Dr. Torrey added, including its retrospective design and the use of a self-report questionnaire to assess psychotic experiences in adulthood.

Also commenting on findings, James Kirkbride, PhD, professor of psychiatric and social epidemiology, University College London, noted the same limitations.

Dr. Kirkbride is the lead author of a 2017 study that showed no link between cat ownership and serious mental illness that included nearly 5,000 people born in 1991 or 1992 and followed until age 18. In this study, there was no link between psychosis and cat ownership during pregnancy or at ages 4 or 10 years.

“Researchers have long been fascinated with the idea that cat ownership may affect mental health. This paper may have them chasing their own tail,” Dr. Kirkbride said.

“Evidence of any association is limited to certain subgroups without a strong theoretical basis for why this may be the case,” he added. “The retrospective and cross-sectional nature of the survey also raise the possibility that the results are impacted by differential recall bias, as well as the broader issues of chance and unobserved confounding.”

Dr. King noted that recall bias is a limitation the researchers highlighted in their study, but “considering the exposures are relatively objective and factual, we do not believe the potential for recall bias is substantial.”

“Nonetheless, we strongly believe that replication of our results in prospective, population-representative cohorts will be crucial to making firmer conclusions,” he added.

The study was funded by grants from the Quebec Health Research Fund. The study authors and Dr. Kirkbride disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori) —the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.

The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H. pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.

In 1971, then-President Nixon declared “war on cancer” (the second leading cause of death in the United States) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.

Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.

Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.

Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.

“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”

A version of this article first appeared on Medscape.com.

From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori) —the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.

The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H. pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.

In 1971, then-President Nixon declared “war on cancer” (the second leading cause of death in the United States) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.

Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.

Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.

Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.

“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”

A version of this article first appeared on Medscape.com.

From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori) —the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.

The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H. pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.

In 1971, then-President Nixon declared “war on cancer” (the second leading cause of death in the United States) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.

Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.

Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.

Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.

“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”

A version of this article first appeared on Medscape.com.

This has been an unfortunate, but not an atypical year, for the children in Maine whose lives have intersected with the state’s Department of Health and Human Services. In 2021, 25 children died of abuse and neglect or in homes with prior involvement with the child protective system. Four cases not included in that number are currently listed as homicides. At a recent legislative hearing the grandmother of one of those victims told her story to the lawmaker.

Her grandson was removed from his mother’s custody at 3 months of age after a 2-year-old sibling overdosed on methadone. Father and grandmother became his caregivers but when the father was arrested the child was returned to the mother’s custody by a judge despite the pleas of the child’s court-appointed guardian. The child eventually returned to the care of his paternal aunt and father, but when the father was arrested again the then 3-year-old was returned to his mother. Within months he was dead with multiple fractures, including to his spine and with internal and intracranial bleeding (Overton P. Maine’s child welfare system failed a 3-year old who died, grandmother tells lawmakers. 2022 Feb 11. Portland Press Herald).

The grandmother questioned the legislators why a vulnerable child would be returned to the care of a woman with such an extensive history of involvement with the Department of Health and Human Services. While there may have been errors of judgment on the part of department staff, in large part the answer lies in the system’s emphasis on reunification. Like apple pie, motherhood, and more recently fatherhood, have been viewed as something deserving of our unquestioning efforts to preserve.

This is not a recent trend. Some of the most frustrating cases over my 40 years of practice involved the failure of the courts and in some cases social workers to place a child’s welfare in the proper perspective as court schedules and custody decisions were made. Too often the reunification of “the family” seemed to trump the needs of the child. Fortunately, I’m unaware of any of my patients who died as the result of these untimely and poorly made decisions. However, many of my patients lived in unsettled conditions never sure what the next week would bring while the system focused on giving an adult whose life was a mess one more chance to demonstrate his or her ability to parent.

Of course, there are occasions in which child protective workers have been too hasty in pulling a child from his or her parents. But, in my experience those cases pale next to the number of times in which children were exposed to home environments that threatened their psychological health and development. Yes, there are bad foster homes. Many foster homes might do a better job if they were working in a system that put a higher value on the emotional needs and safety of the children in making its custody decisions.

We have a governor here in Maine who has worked hard to do the right thing during the pandemic and has made child health a focus. However, her recent proposed appropriations bill appears to continue the focus on reunification by funneling money into programs such as family reunion training and coaching as well as a parent mentorship program. Certainly, one can’t argue that these kind of programs might be helpful to some families. On the other hand, we can’t let these programs create the impression that an intact family is our primary goal. Not every family is repairable, at least on a time schedule compatible with the emotional and health needs of the children.

I wouldn’t be surprised to learn that many of you have experienced a similar frustration when decisions based on an unrealistic goal of family reunification have put your patients at risk.

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].

This has been an unfortunate, but not an atypical year, for the children in Maine whose lives have intersected with the state’s Department of Health and Human Services. In 2021, 25 children died of abuse and neglect or in homes with prior involvement with the child protective system. Four cases not included in that number are currently listed as homicides. At a recent legislative hearing the grandmother of one of those victims told her story to the lawmaker.

Her grandson was removed from his mother’s custody at 3 months of age after a 2-year-old sibling overdosed on methadone. Father and grandmother became his caregivers but when the father was arrested the child was returned to the mother’s custody by a judge despite the pleas of the child’s court-appointed guardian. The child eventually returned to the care of his paternal aunt and father, but when the father was arrested again the then 3-year-old was returned to his mother. Within months he was dead with multiple fractures, including to his spine and with internal and intracranial bleeding (Overton P. Maine’s child welfare system failed a 3-year old who died, grandmother tells lawmakers. 2022 Feb 11. Portland Press Herald).

The grandmother questioned the legislators why a vulnerable child would be returned to the care of a woman with such an extensive history of involvement with the Department of Health and Human Services. While there may have been errors of judgment on the part of department staff, in large part the answer lies in the system’s emphasis on reunification. Like apple pie, motherhood, and more recently fatherhood, have been viewed as something deserving of our unquestioning efforts to preserve.

This is not a recent trend. Some of the most frustrating cases over my 40 years of practice involved the failure of the courts and in some cases social workers to place a child’s welfare in the proper perspective as court schedules and custody decisions were made. Too often the reunification of “the family” seemed to trump the needs of the child. Fortunately, I’m unaware of any of my patients who died as the result of these untimely and poorly made decisions. However, many of my patients lived in unsettled conditions never sure what the next week would bring while the system focused on giving an adult whose life was a mess one more chance to demonstrate his or her ability to parent.

Of course, there are occasions in which child protective workers have been too hasty in pulling a child from his or her parents. But, in my experience those cases pale next to the number of times in which children were exposed to home environments that threatened their psychological health and development. Yes, there are bad foster homes. Many foster homes might do a better job if they were working in a system that put a higher value on the emotional needs and safety of the children in making its custody decisions.

We have a governor here in Maine who has worked hard to do the right thing during the pandemic and has made child health a focus. However, her recent proposed appropriations bill appears to continue the focus on reunification by funneling money into programs such as family reunion training and coaching as well as a parent mentorship program. Certainly, one can’t argue that these kind of programs might be helpful to some families. On the other hand, we can’t let these programs create the impression that an intact family is our primary goal. Not every family is repairable, at least on a time schedule compatible with the emotional and health needs of the children.

I wouldn’t be surprised to learn that many of you have experienced a similar frustration when decisions based on an unrealistic goal of family reunification have put your patients at risk.

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].

This has been an unfortunate, but not an atypical year, for the children in Maine whose lives have intersected with the state’s Department of Health and Human Services. In 2021, 25 children died of abuse and neglect or in homes with prior involvement with the child protective system. Four cases not included in that number are currently listed as homicides. At a recent legislative hearing the grandmother of one of those victims told her story to the lawmaker.

Her grandson was removed from his mother’s custody at 3 months of age after a 2-year-old sibling overdosed on methadone. Father and grandmother became his caregivers but when the father was arrested the child was returned to the mother’s custody by a judge despite the pleas of the child’s court-appointed guardian. The child eventually returned to the care of his paternal aunt and father, but when the father was arrested again the then 3-year-old was returned to his mother. Within months he was dead with multiple fractures, including to his spine and with internal and intracranial bleeding (Overton P. Maine’s child welfare system failed a 3-year old who died, grandmother tells lawmakers. 2022 Feb 11. Portland Press Herald).

The grandmother questioned the legislators why a vulnerable child would be returned to the care of a woman with such an extensive history of involvement with the Department of Health and Human Services. While there may have been errors of judgment on the part of department staff, in large part the answer lies in the system’s emphasis on reunification. Like apple pie, motherhood, and more recently fatherhood, have been viewed as something deserving of our unquestioning efforts to preserve.

This is not a recent trend. Some of the most frustrating cases over my 40 years of practice involved the failure of the courts and in some cases social workers to place a child’s welfare in the proper perspective as court schedules and custody decisions were made. Too often the reunification of “the family” seemed to trump the needs of the child. Fortunately, I’m unaware of any of my patients who died as the result of these untimely and poorly made decisions. However, many of my patients lived in unsettled conditions never sure what the next week would bring while the system focused on giving an adult whose life was a mess one more chance to demonstrate his or her ability to parent.

Of course, there are occasions in which child protective workers have been too hasty in pulling a child from his or her parents. But, in my experience those cases pale next to the number of times in which children were exposed to home environments that threatened their psychological health and development. Yes, there are bad foster homes. Many foster homes might do a better job if they were working in a system that put a higher value on the emotional needs and safety of the children in making its custody decisions.

We have a governor here in Maine who has worked hard to do the right thing during the pandemic and has made child health a focus. However, her recent proposed appropriations bill appears to continue the focus on reunification by funneling money into programs such as family reunion training and coaching as well as a parent mentorship program. Certainly, one can’t argue that these kind of programs might be helpful to some families. On the other hand, we can’t let these programs create the impression that an intact family is our primary goal. Not every family is repairable, at least on a time schedule compatible with the emotional and health needs of the children.

I wouldn’t be surprised to learn that many of you have experienced a similar frustration when decisions based on an unrealistic goal of family reunification have put your patients at risk.

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].

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

A version of this article first appeared on Medscape.com.

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

A version of this article first appeared on Medscape.com.

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

A version of this article first appeared on Medscape.com.

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

A version of this article first appeared on Medscape.com.

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

A version of this article first appeared on Medscape.com.

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

A version of this article first appeared on Medscape.com.

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.

These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.

“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.

The study was published online Jan. 20 in Frontiers in Psychiatry.
 

Anxiety a key driver?

GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.

Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.

“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.

The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).

The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).

ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.

Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.

TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
 

Links to GI disturbance, behavior

Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.

As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).

However, rates of GI disturbances in children with ASD were similar to those with DD.

Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.

Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.

Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.

They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.

The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.

The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
 

First exploration

However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”

The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.

The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.

Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.

The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”

The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.

A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.

The study received funding from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.

These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.

“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.

The study was published online Jan. 20 in Frontiers in Psychiatry.
 

Anxiety a key driver?

GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.

Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.

“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.

The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).

The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).

ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.

Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.

TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
 

Links to GI disturbance, behavior

Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.

As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).

However, rates of GI disturbances in children with ASD were similar to those with DD.

Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.

Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.

Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.

They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.

The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.

The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
 

First exploration

However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”

The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.

The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.

Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.

The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”

The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.

A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.

The study received funding from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.

These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.

“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.

The study was published online Jan. 20 in Frontiers in Psychiatry.
 

Anxiety a key driver?

GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.

Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.

“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.

The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).

The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).

ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.

Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.

TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
 

Links to GI disturbance, behavior

Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.

As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).

However, rates of GI disturbances in children with ASD were similar to those with DD.

Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.

Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.

Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.

They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.

The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.

The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
 

First exploration

However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”

The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.

The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.

Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.

The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”

The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.

A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.

The study received funding from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

A version of this article first appeared on Medscape.com.

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

A version of this article first appeared on Medscape.com.

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

A version of this article first appeared on Medscape.com.