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Concussion increases risk of mental health issues in children
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
FROM JAMA NETWORK OPEN
Managing overuse of food IgE panels: Multiple approaches needed
PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.
Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.
“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.
At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.
The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.
Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”
To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”
In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.
The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.
But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.
On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.
Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”
Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”
The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”
Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”
Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.
A version of this article first appeared on Medscape.com.
PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.
Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.
“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.
At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.
The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.
Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”
To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”
In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.
The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.
But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.
On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.
Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”
Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”
The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”
Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”
Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.
A version of this article first appeared on Medscape.com.
PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.
Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.
“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.
At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.
The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.
Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”
To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”
In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.
The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.
But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.
On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.
Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”
Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”
The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”
Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”
Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.
A version of this article first appeared on Medscape.com.
Depression, suicidal ideation continue to plague physicians: Survey
Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.
In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.
Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.
One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.
Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.
“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
Fighting the stigma of seeking mental health help
Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.
“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”
This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.
“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”
As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
Addressing barriers to mental health
The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”
In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.
Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”
According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.
“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”
A version of this article first appeared on Medscape.com.
Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.
In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.
Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.
One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.
Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.
“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
Fighting the stigma of seeking mental health help
Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.
“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”
This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.
“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”
As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
Addressing barriers to mental health
The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”
In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.
Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”
According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.
“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”
A version of this article first appeared on Medscape.com.
Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.
In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.
Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.
One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.
Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.
“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
Fighting the stigma of seeking mental health help
Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.
“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”
This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.
“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”
As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
Addressing barriers to mental health
The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”
In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.
Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”
According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.
“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”
A version of this article first appeared on Medscape.com.
Routine pharmacogenetic testing in psychiatry not indicated
LAS VEGAS –
“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”
According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”
Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”
Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.
“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.
The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.
Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.
“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”
Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.
In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.
Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.
LAS VEGAS –
“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”
According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”
Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”
Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.
“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.
The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.
Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.
“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”
Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.
In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.
Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.
LAS VEGAS –
“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”
According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”
Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”
Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.
“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.
The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.
Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.
“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”
Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.
In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.
Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.
REPORTING FROM NPA 2022
What is the psychological impact of type 1 diabetes?
“Living with diabetes is not smooth sailing…From the onset of the disease in a child or adolescent through all the days that follow, there is nothing ordinary about it,” according to Aide aux Jeunes Diabétiques (AJD), a French association providing support for children and adolescents with diabetes. What is the psychological impact of the disease on patients and their loved ones? When we look at the life of a person with diabetes, are there key stages that call for more focused attention?
Nadine Hoffmeister, a psychologist at AJD, offers support to patients with diabetes and their parents as they navigate and deal with in-patient treatment for the disease. She recently spoke with this news organization.
Q: Are psychological issues more prevalent in patients with type 1 diabetes (T1D) than in the general population?
Dr. Hoffmeister: Having a chronic disease is not something that should be viewed as automatically making the person more susceptible to psychological issues. When we think about kids with T1D, it’s important to keep in mind that the risk for depression and the risk for eating disorders are, in general, higher in adolescence.
Of course, Clearly, the risk for eating disorders is there, given the constant focus on managing one’s diet. And there’s a greater risk for depression, because life with diabetes can really be trying. That said, how much impact the disease has depends in large part on the environment, the monitoring, and the collaboration of everyone involved.
Q: Are there key stages in the life of patients with T1D that call for targeted psychological support?
Dr. Hoffmeister: The thing about T1D is that it can affect anyone at any age – a small child, a teenager, a young adult. So, in that sense, all ‘firsts’ are key stages. They start, of course, with the first ‘first’: diagnosis. For children diagnosed at an early age, there’s the first day of nursery school or kindergarten, the first piece of birthday cake. Then we get to kids starting middle school and high school, places where they’re now left to their own devices. This is when, for the first time, they’ll have an opportunity to take a trip without their parents and siblings, to go to a party.
And then, there’s the first time using a particular treatment. For example, switching from injections to a pump requires not only an adjustment in terms of physically operating a new device, but a reorientation in terms of mentally settling into a new routine, a new way of administering medication, and so on. They have to learn how to get along with this machine that’s attached to them all the time. They have to view it as being a part of them, view it as a partner, a teammate, a friend. It’s not that easy.
Later on, one of the major stages is, of course, adolescence. Critical developments in the separation–individuation process are taking place. They start to feel the need to break free, to become autonomous, as they seek to fully come to terms with their disease.
Parents usually worry about this stage, adolescence. They’re scared that their child won’t be as vigilant, that they’ll be scatterbrained or careless when it comes to staying on top of all those things that need to be done to keep T1D under control. Most of the time, this stage goes better than they thought. Still, the fact remains that it’s difficult to find a happy medium between adolescence and diabetes. Indeed, there’s a bit of a paradox here. On the one hand, we have adolescence which, by definition, is a time of spontaneity, independence, of trying new things. On the other hand, we have diabetes and its limits and constraints, its care and treatment, day in and day out. We have to pay close attention to how the child navigates and makes their way through this stage of their life.
During adolescence, there’s also a heightened awareness and concern about how others look at you, see you – everywhere, not only in classrooms and hallways. If the way someone looks at them seems aggressive or intrusive, the child may start to feel scared. The risk then becomes that they’ll start feeling awkward or ashamed or embarrassed. We have to keep this in mind and help lead the child away from those feelings. Otherwise, they can end up with low self-esteem, they can start to withdraw.
It can sometimes get to the point where they choose to neglect their treatment so as to conform to the way others see them. Adults can easily lose sight of these kinds of things. So, it’s imperative that we talk to the child. If they’re having trouble following their treatment plan, maybe there’s something going on at school. So, let’s ask them: “How do you like your classes and teachers?” “How are you doing with your injections? Are you finding that they’re getting easier and easier to do?” And always keeping in mind the real possibility that the child may be feeling awkward, ashamed, embarrassed.
Q: Is enough being done to pick up on and address these children’s needs?
Dr. Hoffmeister: I think that these efforts are becoming more and more widespread. Still, there are disparities. When it comes to patients with chronic diseases, it’s not always easy to implement mental health care into the treatment plan. In some cases, there might not be a hospital nearby. And as we know, there are no spots available in medical and psychiatric centers. Of course, outside of hospital settings, we’re seeing the unfortunate situation of fewer and fewer middle schools and high schools having nurses on site.
And then, what options there are for getting support vary greatly from hospital to hospital. Some don’t have psychologists. Others have full schedules and not enough staff. That said, more and more teams are trying to set up regular appointments right from the time of diagnosis. This is a really good approach to take, even though the circumstances may not be ideal. After all, the person has just been told that they have diabetes; they’re not really in the best state of mind to have any kind of discussion.
Q: And so, it makes sense that AJD would offer the kind of mental health support that you’re now providing there.
Dr. Hoffmeister: Exactly. My position was created 4 years ago. I’m not at the hospital. I’m an external. The goal is to be able to offer this psychological support to everyone. I do consultations over the phone so that no matter where a person is in France, they’ll have access to this support. There’s great demand, and the requests are only increasing. I think this has to do with the fact that people are being diagnosed younger and younger. It’s a very complicated situation for the parents. No matter how young their child is, they want to get that support underway as soon as possible.
Q: You speak about the patients getting support. But doesn’t some kind of help have to be given to their parents and loved ones as well?
Dr. Hoffmeister: Yes. I’d say that 60% to 70% of the work I do at AJD is for parents. I also have some older adolescents and some younger kids whom I call to keep up with. But children aren’t very interested in discussing plans over the phone. For parents, the thing about diabetes is that they find themselves in these situations where their child is in the hospital for, say, a week, then is discharged, and all of a sudden, they find themselves at home as the ones in charge of their child’s treatment.
When it’s a little kid, the parents are the ones who are taking care of all the steps, the injections, the pumps. They’re dealing with the distress of a child going through episodes of nocturnal hypoglycemia. They’re experiencing varying degrees of anxiety in carrying out all of these responsibilities and, at the same time, the bond they have with their child is becoming stronger and stronger. So, there’s that anxiety. In this situation, parents may also feel a need for control. And they’re also feeling exhausted; the mental load of dealing with diabetes is very, very intense. To work through all this, many parents reach out for psychological support.
Then later on, when the child has gotten a little older, the parents find it difficult to get to the point of being able to just let go. But once the parents get to know their child better, get to know how their child experiences diabetes, they’ll get to that point. What they come to learn is that the child can take care of things, the child can feel what’s going on in their body, the child can be trusted.
Q: How can we help and support children with diabetes?
Dr. Hoffmeister: One of the most important things is to teach the child to come to terms with the disease and how it affects their body. In other words, the idea here is to adapt diabetes to one’s life, not the other way around. The goal is to not let diabetes take over.
When faced with standardized medical protocols, during a session with a psychologist, the child can talk about their life, give an idea of what a day in their life looks like. For example, the school cafeteria is a place where children get the opportunity to socialize and interact with their peers. We want to have that lunch period be as normal as possible for the child with diabetes. In some schools, lunchtime becomes a challenge. So, not seeing any other solution, mom stops working so the child can come home to eat. These are the kinds of situations where efforts to make the child feel included have failed. They’re tough to deal with, all around. And so this is why we do all we can to keep things as normal as possible for these children.
Q: What would you say is the one initiative out there that’s giving young patients with T1D the most help and support?
Dr. Hoffmeister: AJD offers stays at Care Management and Rehabilitation (SSR) sites. For kids and teenagers with diabetes, these places are like summer camps where every aspect of treatment is taken care of.
There’s a medical team monitoring their disease and a team of counselors always on hand. It’s a time when children may very well bring up things that are on their mind. All in all, the children have a safe and welcoming environment where treatment is provided and they can feel free to open up and talk.
If a problem crops up, I’m always on call to jump online. And throughout the stay, the medical team is keeping in touch to discuss the child’s care.
AJD is also an interdisciplinary association. We regularly organize practice exchange groups that bring together health care professionals and families from all over France. In this way, we’re able to collaborate and come up with resources, such as information packets and kits – for the newly diagnosed, for those starting intensive insulin therapy, and so on. These resources take into account medical protocols related to diabetes. They’re also designed with family life in mind. And having this set of resources works toward standardizing treatments.
A version of this article first appeared on Medscape.com.
“Living with diabetes is not smooth sailing…From the onset of the disease in a child or adolescent through all the days that follow, there is nothing ordinary about it,” according to Aide aux Jeunes Diabétiques (AJD), a French association providing support for children and adolescents with diabetes. What is the psychological impact of the disease on patients and their loved ones? When we look at the life of a person with diabetes, are there key stages that call for more focused attention?
Nadine Hoffmeister, a psychologist at AJD, offers support to patients with diabetes and their parents as they navigate and deal with in-patient treatment for the disease. She recently spoke with this news organization.
Q: Are psychological issues more prevalent in patients with type 1 diabetes (T1D) than in the general population?
Dr. Hoffmeister: Having a chronic disease is not something that should be viewed as automatically making the person more susceptible to psychological issues. When we think about kids with T1D, it’s important to keep in mind that the risk for depression and the risk for eating disorders are, in general, higher in adolescence.
Of course, Clearly, the risk for eating disorders is there, given the constant focus on managing one’s diet. And there’s a greater risk for depression, because life with diabetes can really be trying. That said, how much impact the disease has depends in large part on the environment, the monitoring, and the collaboration of everyone involved.
Q: Are there key stages in the life of patients with T1D that call for targeted psychological support?
Dr. Hoffmeister: The thing about T1D is that it can affect anyone at any age – a small child, a teenager, a young adult. So, in that sense, all ‘firsts’ are key stages. They start, of course, with the first ‘first’: diagnosis. For children diagnosed at an early age, there’s the first day of nursery school or kindergarten, the first piece of birthday cake. Then we get to kids starting middle school and high school, places where they’re now left to their own devices. This is when, for the first time, they’ll have an opportunity to take a trip without their parents and siblings, to go to a party.
And then, there’s the first time using a particular treatment. For example, switching from injections to a pump requires not only an adjustment in terms of physically operating a new device, but a reorientation in terms of mentally settling into a new routine, a new way of administering medication, and so on. They have to learn how to get along with this machine that’s attached to them all the time. They have to view it as being a part of them, view it as a partner, a teammate, a friend. It’s not that easy.
Later on, one of the major stages is, of course, adolescence. Critical developments in the separation–individuation process are taking place. They start to feel the need to break free, to become autonomous, as they seek to fully come to terms with their disease.
Parents usually worry about this stage, adolescence. They’re scared that their child won’t be as vigilant, that they’ll be scatterbrained or careless when it comes to staying on top of all those things that need to be done to keep T1D under control. Most of the time, this stage goes better than they thought. Still, the fact remains that it’s difficult to find a happy medium between adolescence and diabetes. Indeed, there’s a bit of a paradox here. On the one hand, we have adolescence which, by definition, is a time of spontaneity, independence, of trying new things. On the other hand, we have diabetes and its limits and constraints, its care and treatment, day in and day out. We have to pay close attention to how the child navigates and makes their way through this stage of their life.
During adolescence, there’s also a heightened awareness and concern about how others look at you, see you – everywhere, not only in classrooms and hallways. If the way someone looks at them seems aggressive or intrusive, the child may start to feel scared. The risk then becomes that they’ll start feeling awkward or ashamed or embarrassed. We have to keep this in mind and help lead the child away from those feelings. Otherwise, they can end up with low self-esteem, they can start to withdraw.
It can sometimes get to the point where they choose to neglect their treatment so as to conform to the way others see them. Adults can easily lose sight of these kinds of things. So, it’s imperative that we talk to the child. If they’re having trouble following their treatment plan, maybe there’s something going on at school. So, let’s ask them: “How do you like your classes and teachers?” “How are you doing with your injections? Are you finding that they’re getting easier and easier to do?” And always keeping in mind the real possibility that the child may be feeling awkward, ashamed, embarrassed.
Q: Is enough being done to pick up on and address these children’s needs?
Dr. Hoffmeister: I think that these efforts are becoming more and more widespread. Still, there are disparities. When it comes to patients with chronic diseases, it’s not always easy to implement mental health care into the treatment plan. In some cases, there might not be a hospital nearby. And as we know, there are no spots available in medical and psychiatric centers. Of course, outside of hospital settings, we’re seeing the unfortunate situation of fewer and fewer middle schools and high schools having nurses on site.
And then, what options there are for getting support vary greatly from hospital to hospital. Some don’t have psychologists. Others have full schedules and not enough staff. That said, more and more teams are trying to set up regular appointments right from the time of diagnosis. This is a really good approach to take, even though the circumstances may not be ideal. After all, the person has just been told that they have diabetes; they’re not really in the best state of mind to have any kind of discussion.
Q: And so, it makes sense that AJD would offer the kind of mental health support that you’re now providing there.
Dr. Hoffmeister: Exactly. My position was created 4 years ago. I’m not at the hospital. I’m an external. The goal is to be able to offer this psychological support to everyone. I do consultations over the phone so that no matter where a person is in France, they’ll have access to this support. There’s great demand, and the requests are only increasing. I think this has to do with the fact that people are being diagnosed younger and younger. It’s a very complicated situation for the parents. No matter how young their child is, they want to get that support underway as soon as possible.
Q: You speak about the patients getting support. But doesn’t some kind of help have to be given to their parents and loved ones as well?
Dr. Hoffmeister: Yes. I’d say that 60% to 70% of the work I do at AJD is for parents. I also have some older adolescents and some younger kids whom I call to keep up with. But children aren’t very interested in discussing plans over the phone. For parents, the thing about diabetes is that they find themselves in these situations where their child is in the hospital for, say, a week, then is discharged, and all of a sudden, they find themselves at home as the ones in charge of their child’s treatment.
When it’s a little kid, the parents are the ones who are taking care of all the steps, the injections, the pumps. They’re dealing with the distress of a child going through episodes of nocturnal hypoglycemia. They’re experiencing varying degrees of anxiety in carrying out all of these responsibilities and, at the same time, the bond they have with their child is becoming stronger and stronger. So, there’s that anxiety. In this situation, parents may also feel a need for control. And they’re also feeling exhausted; the mental load of dealing with diabetes is very, very intense. To work through all this, many parents reach out for psychological support.
Then later on, when the child has gotten a little older, the parents find it difficult to get to the point of being able to just let go. But once the parents get to know their child better, get to know how their child experiences diabetes, they’ll get to that point. What they come to learn is that the child can take care of things, the child can feel what’s going on in their body, the child can be trusted.
Q: How can we help and support children with diabetes?
Dr. Hoffmeister: One of the most important things is to teach the child to come to terms with the disease and how it affects their body. In other words, the idea here is to adapt diabetes to one’s life, not the other way around. The goal is to not let diabetes take over.
When faced with standardized medical protocols, during a session with a psychologist, the child can talk about their life, give an idea of what a day in their life looks like. For example, the school cafeteria is a place where children get the opportunity to socialize and interact with their peers. We want to have that lunch period be as normal as possible for the child with diabetes. In some schools, lunchtime becomes a challenge. So, not seeing any other solution, mom stops working so the child can come home to eat. These are the kinds of situations where efforts to make the child feel included have failed. They’re tough to deal with, all around. And so this is why we do all we can to keep things as normal as possible for these children.
Q: What would you say is the one initiative out there that’s giving young patients with T1D the most help and support?
Dr. Hoffmeister: AJD offers stays at Care Management and Rehabilitation (SSR) sites. For kids and teenagers with diabetes, these places are like summer camps where every aspect of treatment is taken care of.
There’s a medical team monitoring their disease and a team of counselors always on hand. It’s a time when children may very well bring up things that are on their mind. All in all, the children have a safe and welcoming environment where treatment is provided and they can feel free to open up and talk.
If a problem crops up, I’m always on call to jump online. And throughout the stay, the medical team is keeping in touch to discuss the child’s care.
AJD is also an interdisciplinary association. We regularly organize practice exchange groups that bring together health care professionals and families from all over France. In this way, we’re able to collaborate and come up with resources, such as information packets and kits – for the newly diagnosed, for those starting intensive insulin therapy, and so on. These resources take into account medical protocols related to diabetes. They’re also designed with family life in mind. And having this set of resources works toward standardizing treatments.
A version of this article first appeared on Medscape.com.
“Living with diabetes is not smooth sailing…From the onset of the disease in a child or adolescent through all the days that follow, there is nothing ordinary about it,” according to Aide aux Jeunes Diabétiques (AJD), a French association providing support for children and adolescents with diabetes. What is the psychological impact of the disease on patients and their loved ones? When we look at the life of a person with diabetes, are there key stages that call for more focused attention?
Nadine Hoffmeister, a psychologist at AJD, offers support to patients with diabetes and their parents as they navigate and deal with in-patient treatment for the disease. She recently spoke with this news organization.
Q: Are psychological issues more prevalent in patients with type 1 diabetes (T1D) than in the general population?
Dr. Hoffmeister: Having a chronic disease is not something that should be viewed as automatically making the person more susceptible to psychological issues. When we think about kids with T1D, it’s important to keep in mind that the risk for depression and the risk for eating disorders are, in general, higher in adolescence.
Of course, Clearly, the risk for eating disorders is there, given the constant focus on managing one’s diet. And there’s a greater risk for depression, because life with diabetes can really be trying. That said, how much impact the disease has depends in large part on the environment, the monitoring, and the collaboration of everyone involved.
Q: Are there key stages in the life of patients with T1D that call for targeted psychological support?
Dr. Hoffmeister: The thing about T1D is that it can affect anyone at any age – a small child, a teenager, a young adult. So, in that sense, all ‘firsts’ are key stages. They start, of course, with the first ‘first’: diagnosis. For children diagnosed at an early age, there’s the first day of nursery school or kindergarten, the first piece of birthday cake. Then we get to kids starting middle school and high school, places where they’re now left to their own devices. This is when, for the first time, they’ll have an opportunity to take a trip without their parents and siblings, to go to a party.
And then, there’s the first time using a particular treatment. For example, switching from injections to a pump requires not only an adjustment in terms of physically operating a new device, but a reorientation in terms of mentally settling into a new routine, a new way of administering medication, and so on. They have to learn how to get along with this machine that’s attached to them all the time. They have to view it as being a part of them, view it as a partner, a teammate, a friend. It’s not that easy.
Later on, one of the major stages is, of course, adolescence. Critical developments in the separation–individuation process are taking place. They start to feel the need to break free, to become autonomous, as they seek to fully come to terms with their disease.
Parents usually worry about this stage, adolescence. They’re scared that their child won’t be as vigilant, that they’ll be scatterbrained or careless when it comes to staying on top of all those things that need to be done to keep T1D under control. Most of the time, this stage goes better than they thought. Still, the fact remains that it’s difficult to find a happy medium between adolescence and diabetes. Indeed, there’s a bit of a paradox here. On the one hand, we have adolescence which, by definition, is a time of spontaneity, independence, of trying new things. On the other hand, we have diabetes and its limits and constraints, its care and treatment, day in and day out. We have to pay close attention to how the child navigates and makes their way through this stage of their life.
During adolescence, there’s also a heightened awareness and concern about how others look at you, see you – everywhere, not only in classrooms and hallways. If the way someone looks at them seems aggressive or intrusive, the child may start to feel scared. The risk then becomes that they’ll start feeling awkward or ashamed or embarrassed. We have to keep this in mind and help lead the child away from those feelings. Otherwise, they can end up with low self-esteem, they can start to withdraw.
It can sometimes get to the point where they choose to neglect their treatment so as to conform to the way others see them. Adults can easily lose sight of these kinds of things. So, it’s imperative that we talk to the child. If they’re having trouble following their treatment plan, maybe there’s something going on at school. So, let’s ask them: “How do you like your classes and teachers?” “How are you doing with your injections? Are you finding that they’re getting easier and easier to do?” And always keeping in mind the real possibility that the child may be feeling awkward, ashamed, embarrassed.
Q: Is enough being done to pick up on and address these children’s needs?
Dr. Hoffmeister: I think that these efforts are becoming more and more widespread. Still, there are disparities. When it comes to patients with chronic diseases, it’s not always easy to implement mental health care into the treatment plan. In some cases, there might not be a hospital nearby. And as we know, there are no spots available in medical and psychiatric centers. Of course, outside of hospital settings, we’re seeing the unfortunate situation of fewer and fewer middle schools and high schools having nurses on site.
And then, what options there are for getting support vary greatly from hospital to hospital. Some don’t have psychologists. Others have full schedules and not enough staff. That said, more and more teams are trying to set up regular appointments right from the time of diagnosis. This is a really good approach to take, even though the circumstances may not be ideal. After all, the person has just been told that they have diabetes; they’re not really in the best state of mind to have any kind of discussion.
Q: And so, it makes sense that AJD would offer the kind of mental health support that you’re now providing there.
Dr. Hoffmeister: Exactly. My position was created 4 years ago. I’m not at the hospital. I’m an external. The goal is to be able to offer this psychological support to everyone. I do consultations over the phone so that no matter where a person is in France, they’ll have access to this support. There’s great demand, and the requests are only increasing. I think this has to do with the fact that people are being diagnosed younger and younger. It’s a very complicated situation for the parents. No matter how young their child is, they want to get that support underway as soon as possible.
Q: You speak about the patients getting support. But doesn’t some kind of help have to be given to their parents and loved ones as well?
Dr. Hoffmeister: Yes. I’d say that 60% to 70% of the work I do at AJD is for parents. I also have some older adolescents and some younger kids whom I call to keep up with. But children aren’t very interested in discussing plans over the phone. For parents, the thing about diabetes is that they find themselves in these situations where their child is in the hospital for, say, a week, then is discharged, and all of a sudden, they find themselves at home as the ones in charge of their child’s treatment.
When it’s a little kid, the parents are the ones who are taking care of all the steps, the injections, the pumps. They’re dealing with the distress of a child going through episodes of nocturnal hypoglycemia. They’re experiencing varying degrees of anxiety in carrying out all of these responsibilities and, at the same time, the bond they have with their child is becoming stronger and stronger. So, there’s that anxiety. In this situation, parents may also feel a need for control. And they’re also feeling exhausted; the mental load of dealing with diabetes is very, very intense. To work through all this, many parents reach out for psychological support.
Then later on, when the child has gotten a little older, the parents find it difficult to get to the point of being able to just let go. But once the parents get to know their child better, get to know how their child experiences diabetes, they’ll get to that point. What they come to learn is that the child can take care of things, the child can feel what’s going on in their body, the child can be trusted.
Q: How can we help and support children with diabetes?
Dr. Hoffmeister: One of the most important things is to teach the child to come to terms with the disease and how it affects their body. In other words, the idea here is to adapt diabetes to one’s life, not the other way around. The goal is to not let diabetes take over.
When faced with standardized medical protocols, during a session with a psychologist, the child can talk about their life, give an idea of what a day in their life looks like. For example, the school cafeteria is a place where children get the opportunity to socialize and interact with their peers. We want to have that lunch period be as normal as possible for the child with diabetes. In some schools, lunchtime becomes a challenge. So, not seeing any other solution, mom stops working so the child can come home to eat. These are the kinds of situations where efforts to make the child feel included have failed. They’re tough to deal with, all around. And so this is why we do all we can to keep things as normal as possible for these children.
Q: What would you say is the one initiative out there that’s giving young patients with T1D the most help and support?
Dr. Hoffmeister: AJD offers stays at Care Management and Rehabilitation (SSR) sites. For kids and teenagers with diabetes, these places are like summer camps where every aspect of treatment is taken care of.
There’s a medical team monitoring their disease and a team of counselors always on hand. It’s a time when children may very well bring up things that are on their mind. All in all, the children have a safe and welcoming environment where treatment is provided and they can feel free to open up and talk.
If a problem crops up, I’m always on call to jump online. And throughout the stay, the medical team is keeping in touch to discuss the child’s care.
AJD is also an interdisciplinary association. We regularly organize practice exchange groups that bring together health care professionals and families from all over France. In this way, we’re able to collaborate and come up with resources, such as information packets and kits – for the newly diagnosed, for those starting intensive insulin therapy, and so on. These resources take into account medical protocols related to diabetes. They’re also designed with family life in mind. And having this set of resources works toward standardizing treatments.
A version of this article first appeared on Medscape.com.
Mechanical ventilation in children tied to slightly lower IQ
Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.
Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.
Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.
“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.
The study was published online March 1 in JAMA.
Unknown long-term effects
“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.
“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.
Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.
To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.
For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.
To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.
Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.
The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
‘Uncertain’ clinical importance
Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.
Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.
The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.
The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.
Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.
Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.
Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.
“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.
The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”
Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
Filling a research gap
Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”
Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”
The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.
The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.
Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.
Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.
“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.
The study was published online March 1 in JAMA.
Unknown long-term effects
“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.
“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.
Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.
To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.
For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.
To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.
Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.
The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
‘Uncertain’ clinical importance
Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.
Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.
The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.
The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.
Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.
Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.
Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.
“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.
The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”
Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
Filling a research gap
Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”
Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”
The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.
The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.
Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.
Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.
“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.
The study was published online March 1 in JAMA.
Unknown long-term effects
“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.
“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.
Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.
To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.
For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.
To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.
Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.
The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
‘Uncertain’ clinical importance
Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.
Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.
The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.
The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.
Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.
Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.
Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.
“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.
The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”
Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
Filling a research gap
Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”
Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”
The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.
The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA
Beware of the latest TikTok trend: Nasal spray tans
Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.
The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.
“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”
Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.
The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.
In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.
But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.
“Don’t try this at home,” said Dr. Talakoub.
“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”
It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.
Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”
@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.
TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.
The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.
“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.
“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.
“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”
At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.
Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.
“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”
He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.
“At the end of the day, just don’t inhale,” Dr. Friedman said.
A version of this article first appeared on WebMD.com.
Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.
The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.
“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”
Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.
The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.
In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.
But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.
“Don’t try this at home,” said Dr. Talakoub.
“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”
It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.
Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”
@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.
TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.
The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.
“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.
“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.
“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”
At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.
Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.
“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”
He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.
“At the end of the day, just don’t inhale,” Dr. Friedman said.
A version of this article first appeared on WebMD.com.
Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.
The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.
“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”
Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.
The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.
In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.
But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.
“Don’t try this at home,” said Dr. Talakoub.
“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”
It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.
Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”
@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.
TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.
The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.
“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.
“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.
“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”
At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.
Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.
“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”
He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.
“At the end of the day, just don’t inhale,” Dr. Friedman said.
A version of this article first appeared on WebMD.com.
Nirsevimab protects healthy infants from RSV
A single injection of the experimental agent nirsevimab ahead of respiratory syncytial virus (RSV) season protects healthy infants from lower respiratory tract infections associated with the pathogen, according to the results of a phase 3 study.
A previously published trial showed that a single dose of nirsevimab was effective in preterm infants. The ability to protect all babies from RSV, which causes bronchiolitis and pneumonia and is a leading cause of hospitalization for this age group, “would be a paradigm shift in the approach to this disease,” William Muller, MD, PhD, of the Lurie Children’s Hospital of Chicago and a coauthor of the study, said in a statement.
The primary endpoint of the study was medically attended lower respiratory tract infections linked to RSV. The single injection of nirsevimab was associated with a 74.5% reduction in such infections (P < .001), according to Dr. Muller’s group, who published their findings March 2 in the New England Journal of Medicine.
Nirsevimab, a monoclonal antibody to the RSV fusion protein being developed by AstraZeneca and Sanofi, has an extended half-life, which may allow one dose to confer protection throughout a season. The only approved option to prevent RSV, palivizumab (Synagis), is used for high-risk infants, and five injections are needed to cover a viral season.
Nearly 1,500 infants in more than 20 countries studied
To assess the effectiveness of nirsevimab in late-preterm and term infants, investigators at 160 sites randomly assigned 1,490 babies born at a gestational age of at least 35 weeks to receive an intramuscular injection of nirsevimab or placebo.
During the 150 days after injection, medically attended RSV-associated lower respiratory tract infections occurred in 12 of 994 infants who received nirsevimab, compared with 25 of 496 babies who received placebo (1.2% vs. 5%).
Six of 994 infants who received nirsevimab were hospitalized for RSV-associated lower respiratory tract infections, compared with 8 of 496 infants in the placebo group (0.6% vs. 1.6%; P = .07). The proportion of children hospitalized for any respiratory illness as a result of RSV was 0.9% among those who received nirsevimab, compared with 2.2% among those who received placebo.
Serious adverse events occurred in 6.8% of the nirsevimab group and 7.3% of the placebo group. None of these events, including three deaths in the nirsevimab group, was considered related to nirsevimab or placebo, according to the researchers. One infant who received nirsevimab had a generalized macular rash without systemic features that did not require treatment and resolved in 20 days, they said.
Antidrug antibodies were detected in 6.1% of the nirsevimab group and in 1.1% of the placebo group. These antidrug antibodies tended to develop later and did not affect nirsevimab pharmacokinetics during the RSV season, the researchers reported. How they might affect subsequent doses of nirsevimab is not known, they added.
In a separate report in the journal, researcher Joseph Domachowske, MD, SUNY Upstate Medical University, Syracuse, New York, and colleagues described safety results from an ongoing study of nirsevimab that includes infants with congenital heart disease, chronic lung disease, and prematurity.
In this trial, infants received nirsevimab or palivizumab, and the treatments appeared to have similar safety profiles, the authors reported.
Other approaches to RSV protection include passive antibodies acquired from maternal vaccination in pregnancy and active vaccination of infants.
The publication follows news last month that GlaxoSmithKline is pausing a maternal RSV vaccine trial, which “had the same goal of protecting babies against severe RSV infection,” said Louis Bont, MD, PhD, with University Medical Center Utrecht, the Netherlands.
RSV infection is one of the deadliest diseases during infancy, and the nirsevimab trial, conducted in more than 20 countries, is “gamechanging,” Dr. Bont told this news organization. Still, researchers will need to monitor for RSV resistance to this treatment, he said.
Whether nirsevimab prevents the development of reactive airway disease and asthma is another open question, he said.
“Finally, we need to keep in mind that RSV mortality is almost limited to the developing world, and it is unlikely that this novel drug will become available to these countries in the coming years,” Dr. Bont said. “Nevertheless, nirsevimab has the potential to seriously decrease the annual overwhelming number of RSV infected babies.”
Nirsevimab may have advantages in low- and middle-income countries, including its potential to be incorporated into established immunization programs and to be given seasonally, said Amy Sarah Ginsburg, MD, MPH, of the University of Washington, Seattle. “However, cost remains a significant factor, as does susceptibility to pathogen escape,” she said.
MedImmune/AstraZeneca and Sanofi funded the nirsevimab studies. UMC Utrecht has received research grants and fees for advisory work from AstraZeneca for RSV-related work by Bont.
A version of this article first appeared on Medscape.com.
A single injection of the experimental agent nirsevimab ahead of respiratory syncytial virus (RSV) season protects healthy infants from lower respiratory tract infections associated with the pathogen, according to the results of a phase 3 study.
A previously published trial showed that a single dose of nirsevimab was effective in preterm infants. The ability to protect all babies from RSV, which causes bronchiolitis and pneumonia and is a leading cause of hospitalization for this age group, “would be a paradigm shift in the approach to this disease,” William Muller, MD, PhD, of the Lurie Children’s Hospital of Chicago and a coauthor of the study, said in a statement.
The primary endpoint of the study was medically attended lower respiratory tract infections linked to RSV. The single injection of nirsevimab was associated with a 74.5% reduction in such infections (P < .001), according to Dr. Muller’s group, who published their findings March 2 in the New England Journal of Medicine.
Nirsevimab, a monoclonal antibody to the RSV fusion protein being developed by AstraZeneca and Sanofi, has an extended half-life, which may allow one dose to confer protection throughout a season. The only approved option to prevent RSV, palivizumab (Synagis), is used for high-risk infants, and five injections are needed to cover a viral season.
Nearly 1,500 infants in more than 20 countries studied
To assess the effectiveness of nirsevimab in late-preterm and term infants, investigators at 160 sites randomly assigned 1,490 babies born at a gestational age of at least 35 weeks to receive an intramuscular injection of nirsevimab or placebo.
During the 150 days after injection, medically attended RSV-associated lower respiratory tract infections occurred in 12 of 994 infants who received nirsevimab, compared with 25 of 496 babies who received placebo (1.2% vs. 5%).
Six of 994 infants who received nirsevimab were hospitalized for RSV-associated lower respiratory tract infections, compared with 8 of 496 infants in the placebo group (0.6% vs. 1.6%; P = .07). The proportion of children hospitalized for any respiratory illness as a result of RSV was 0.9% among those who received nirsevimab, compared with 2.2% among those who received placebo.
Serious adverse events occurred in 6.8% of the nirsevimab group and 7.3% of the placebo group. None of these events, including three deaths in the nirsevimab group, was considered related to nirsevimab or placebo, according to the researchers. One infant who received nirsevimab had a generalized macular rash without systemic features that did not require treatment and resolved in 20 days, they said.
Antidrug antibodies were detected in 6.1% of the nirsevimab group and in 1.1% of the placebo group. These antidrug antibodies tended to develop later and did not affect nirsevimab pharmacokinetics during the RSV season, the researchers reported. How they might affect subsequent doses of nirsevimab is not known, they added.
In a separate report in the journal, researcher Joseph Domachowske, MD, SUNY Upstate Medical University, Syracuse, New York, and colleagues described safety results from an ongoing study of nirsevimab that includes infants with congenital heart disease, chronic lung disease, and prematurity.
In this trial, infants received nirsevimab or palivizumab, and the treatments appeared to have similar safety profiles, the authors reported.
Other approaches to RSV protection include passive antibodies acquired from maternal vaccination in pregnancy and active vaccination of infants.
The publication follows news last month that GlaxoSmithKline is pausing a maternal RSV vaccine trial, which “had the same goal of protecting babies against severe RSV infection,” said Louis Bont, MD, PhD, with University Medical Center Utrecht, the Netherlands.
RSV infection is one of the deadliest diseases during infancy, and the nirsevimab trial, conducted in more than 20 countries, is “gamechanging,” Dr. Bont told this news organization. Still, researchers will need to monitor for RSV resistance to this treatment, he said.
Whether nirsevimab prevents the development of reactive airway disease and asthma is another open question, he said.
“Finally, we need to keep in mind that RSV mortality is almost limited to the developing world, and it is unlikely that this novel drug will become available to these countries in the coming years,” Dr. Bont said. “Nevertheless, nirsevimab has the potential to seriously decrease the annual overwhelming number of RSV infected babies.”
Nirsevimab may have advantages in low- and middle-income countries, including its potential to be incorporated into established immunization programs and to be given seasonally, said Amy Sarah Ginsburg, MD, MPH, of the University of Washington, Seattle. “However, cost remains a significant factor, as does susceptibility to pathogen escape,” she said.
MedImmune/AstraZeneca and Sanofi funded the nirsevimab studies. UMC Utrecht has received research grants and fees for advisory work from AstraZeneca for RSV-related work by Bont.
A version of this article first appeared on Medscape.com.
A single injection of the experimental agent nirsevimab ahead of respiratory syncytial virus (RSV) season protects healthy infants from lower respiratory tract infections associated with the pathogen, according to the results of a phase 3 study.
A previously published trial showed that a single dose of nirsevimab was effective in preterm infants. The ability to protect all babies from RSV, which causes bronchiolitis and pneumonia and is a leading cause of hospitalization for this age group, “would be a paradigm shift in the approach to this disease,” William Muller, MD, PhD, of the Lurie Children’s Hospital of Chicago and a coauthor of the study, said in a statement.
The primary endpoint of the study was medically attended lower respiratory tract infections linked to RSV. The single injection of nirsevimab was associated with a 74.5% reduction in such infections (P < .001), according to Dr. Muller’s group, who published their findings March 2 in the New England Journal of Medicine.
Nirsevimab, a monoclonal antibody to the RSV fusion protein being developed by AstraZeneca and Sanofi, has an extended half-life, which may allow one dose to confer protection throughout a season. The only approved option to prevent RSV, palivizumab (Synagis), is used for high-risk infants, and five injections are needed to cover a viral season.
Nearly 1,500 infants in more than 20 countries studied
To assess the effectiveness of nirsevimab in late-preterm and term infants, investigators at 160 sites randomly assigned 1,490 babies born at a gestational age of at least 35 weeks to receive an intramuscular injection of nirsevimab or placebo.
During the 150 days after injection, medically attended RSV-associated lower respiratory tract infections occurred in 12 of 994 infants who received nirsevimab, compared with 25 of 496 babies who received placebo (1.2% vs. 5%).
Six of 994 infants who received nirsevimab were hospitalized for RSV-associated lower respiratory tract infections, compared with 8 of 496 infants in the placebo group (0.6% vs. 1.6%; P = .07). The proportion of children hospitalized for any respiratory illness as a result of RSV was 0.9% among those who received nirsevimab, compared with 2.2% among those who received placebo.
Serious adverse events occurred in 6.8% of the nirsevimab group and 7.3% of the placebo group. None of these events, including three deaths in the nirsevimab group, was considered related to nirsevimab or placebo, according to the researchers. One infant who received nirsevimab had a generalized macular rash without systemic features that did not require treatment and resolved in 20 days, they said.
Antidrug antibodies were detected in 6.1% of the nirsevimab group and in 1.1% of the placebo group. These antidrug antibodies tended to develop later and did not affect nirsevimab pharmacokinetics during the RSV season, the researchers reported. How they might affect subsequent doses of nirsevimab is not known, they added.
In a separate report in the journal, researcher Joseph Domachowske, MD, SUNY Upstate Medical University, Syracuse, New York, and colleagues described safety results from an ongoing study of nirsevimab that includes infants with congenital heart disease, chronic lung disease, and prematurity.
In this trial, infants received nirsevimab or palivizumab, and the treatments appeared to have similar safety profiles, the authors reported.
Other approaches to RSV protection include passive antibodies acquired from maternal vaccination in pregnancy and active vaccination of infants.
The publication follows news last month that GlaxoSmithKline is pausing a maternal RSV vaccine trial, which “had the same goal of protecting babies against severe RSV infection,” said Louis Bont, MD, PhD, with University Medical Center Utrecht, the Netherlands.
RSV infection is one of the deadliest diseases during infancy, and the nirsevimab trial, conducted in more than 20 countries, is “gamechanging,” Dr. Bont told this news organization. Still, researchers will need to monitor for RSV resistance to this treatment, he said.
Whether nirsevimab prevents the development of reactive airway disease and asthma is another open question, he said.
“Finally, we need to keep in mind that RSV mortality is almost limited to the developing world, and it is unlikely that this novel drug will become available to these countries in the coming years,” Dr. Bont said. “Nevertheless, nirsevimab has the potential to seriously decrease the annual overwhelming number of RSV infected babies.”
Nirsevimab may have advantages in low- and middle-income countries, including its potential to be incorporated into established immunization programs and to be given seasonally, said Amy Sarah Ginsburg, MD, MPH, of the University of Washington, Seattle. “However, cost remains a significant factor, as does susceptibility to pathogen escape,” she said.
MedImmune/AstraZeneca and Sanofi funded the nirsevimab studies. UMC Utrecht has received research grants and fees for advisory work from AstraZeneca for RSV-related work by Bont.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Pediatric IBD increases cancer risk later in life
Children who are diagnosed with inflammatory bowel disease (IBD) are more than twice as likely to develop cancer, especially gastrointestinal cancer, later in life compared with the general pediatric population, a new meta-analysis suggests.
Although the overall incidence rate of cancer in this population is low, “we found a 2.4-fold increase in the relative rate of cancer among patients with pediatric-onset IBD compared with the general pediatric population, primarily associated with an increased rate of gastrointestinal cancers,” wrote senior author Tine Jess, MD, DMSci, Aalborg University, Copenhagen, and colleagues.
The study was published online March 1 in JAMA Network Open.
Previous research indicates that IBD is associated with an increased risk for colon, small bowel, and other types of cancer in adults, but the risk among children with IBD is not well understood.
In the current analysis, Dr. Jess and colleagues examined five population-based studies from North America and Europe, which included more than 19,800 participants with pediatric-onset IBD. Of these participants, 715 were later diagnosed with cancer.
Overall, the risk for cancer among individuals with pediatric-onset IBD was 2.4-fold higher than that of their peers without IBD, but those rates varied by IBD subtype. Those with Crohn’s disease, for instance, were about two times more likely to develop cancer, while those with ulcerative colitis were 2.6 times more likely to develop cancer later.
Two studies included in the meta-analysis broke down results by sex and found that the risk for cancer was higher among male versus female patients (pooled relative rates [pRR], 3.23 in men and 2.45 in women).
These two studies also calculated the risk for cancer by exposure to thiopurines. Patients receiving these immunosuppressive drugs had an increased relative rate of cancer (pRR, 2.09). Although numerically higher, this rate was not statistically higher compared with patients not exposed to the drugs (pRR, 1.82).
When looking at risk by cancer site, the authors consistently observed the highest relative rates for gastrointestinal cancers. Specifically, the investigators calculated a 55-fold increased risk for liver cancer (pRR, 55.4), followed by a 20-fold increased risk for colorectal cancer (pRR, 20.2), and a 16-fold increased risk for small bowel cancer (pRR, 16.2).
Despite such high estimates for gastrointestinal cancers, “this risk corresponds to a mean incidence rate of 0.3 cases of liver cancer, 0.6 cases of colorectal cancer, and 0.1 cases of small bowel cancer per 1,000 person-years in this population,” the authors noted.
In other words, “the overall incidence rate of cancer in this population is low,” at less than 3.3 cases per 1,000 person-years, the authors concluded.
Relative rates of extraintestinal cancers were even lower, with the highest risks for nonmelanoma skin cancer (pRR, 3.62), lymphoid cancer (pRR, 3.10), and melanoma (pRR, 2.05).
The authors suggest that identifying variables that might reduce cancer risk in pediatric patients who develop IBD could better shape management and prevention strategies.
CRC screening guidelines already recommend that children undergo a colonoscopy 6-8 years after being diagnosed with colitis extending beyond the rectum. Annual colonoscopy is also recommended for patients with primary sclerosing cholangitis from the time of diagnosis and annual screening for skin cancer is recommended for all patients with IBD.
The investigators further suggest that because ongoing inflammation is an important risk factor for cancer, early and adequate control of inflammation could be critical in the prevention of long-term complications.
The study was supported by a grant from the Danish National Research Foundation. Dr. Jess and coauthors Rahma Elmahdi, MD, Camilla Lemser, and Kristine Allin, MD, reported receiving grants from the Danish National Research Foundation National Center of Excellence during the conduct of the study. Coauthor Manasi Agrawal, MD, reported receiving grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study.
A version of this article first appeared on Medscape.com.
Children who are diagnosed with inflammatory bowel disease (IBD) are more than twice as likely to develop cancer, especially gastrointestinal cancer, later in life compared with the general pediatric population, a new meta-analysis suggests.
Although the overall incidence rate of cancer in this population is low, “we found a 2.4-fold increase in the relative rate of cancer among patients with pediatric-onset IBD compared with the general pediatric population, primarily associated with an increased rate of gastrointestinal cancers,” wrote senior author Tine Jess, MD, DMSci, Aalborg University, Copenhagen, and colleagues.
The study was published online March 1 in JAMA Network Open.
Previous research indicates that IBD is associated with an increased risk for colon, small bowel, and other types of cancer in adults, but the risk among children with IBD is not well understood.
In the current analysis, Dr. Jess and colleagues examined five population-based studies from North America and Europe, which included more than 19,800 participants with pediatric-onset IBD. Of these participants, 715 were later diagnosed with cancer.
Overall, the risk for cancer among individuals with pediatric-onset IBD was 2.4-fold higher than that of their peers without IBD, but those rates varied by IBD subtype. Those with Crohn’s disease, for instance, were about two times more likely to develop cancer, while those with ulcerative colitis were 2.6 times more likely to develop cancer later.
Two studies included in the meta-analysis broke down results by sex and found that the risk for cancer was higher among male versus female patients (pooled relative rates [pRR], 3.23 in men and 2.45 in women).
These two studies also calculated the risk for cancer by exposure to thiopurines. Patients receiving these immunosuppressive drugs had an increased relative rate of cancer (pRR, 2.09). Although numerically higher, this rate was not statistically higher compared with patients not exposed to the drugs (pRR, 1.82).
When looking at risk by cancer site, the authors consistently observed the highest relative rates for gastrointestinal cancers. Specifically, the investigators calculated a 55-fold increased risk for liver cancer (pRR, 55.4), followed by a 20-fold increased risk for colorectal cancer (pRR, 20.2), and a 16-fold increased risk for small bowel cancer (pRR, 16.2).
Despite such high estimates for gastrointestinal cancers, “this risk corresponds to a mean incidence rate of 0.3 cases of liver cancer, 0.6 cases of colorectal cancer, and 0.1 cases of small bowel cancer per 1,000 person-years in this population,” the authors noted.
In other words, “the overall incidence rate of cancer in this population is low,” at less than 3.3 cases per 1,000 person-years, the authors concluded.
Relative rates of extraintestinal cancers were even lower, with the highest risks for nonmelanoma skin cancer (pRR, 3.62), lymphoid cancer (pRR, 3.10), and melanoma (pRR, 2.05).
The authors suggest that identifying variables that might reduce cancer risk in pediatric patients who develop IBD could better shape management and prevention strategies.
CRC screening guidelines already recommend that children undergo a colonoscopy 6-8 years after being diagnosed with colitis extending beyond the rectum. Annual colonoscopy is also recommended for patients with primary sclerosing cholangitis from the time of diagnosis and annual screening for skin cancer is recommended for all patients with IBD.
The investigators further suggest that because ongoing inflammation is an important risk factor for cancer, early and adequate control of inflammation could be critical in the prevention of long-term complications.
The study was supported by a grant from the Danish National Research Foundation. Dr. Jess and coauthors Rahma Elmahdi, MD, Camilla Lemser, and Kristine Allin, MD, reported receiving grants from the Danish National Research Foundation National Center of Excellence during the conduct of the study. Coauthor Manasi Agrawal, MD, reported receiving grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study.
A version of this article first appeared on Medscape.com.
Children who are diagnosed with inflammatory bowel disease (IBD) are more than twice as likely to develop cancer, especially gastrointestinal cancer, later in life compared with the general pediatric population, a new meta-analysis suggests.
Although the overall incidence rate of cancer in this population is low, “we found a 2.4-fold increase in the relative rate of cancer among patients with pediatric-onset IBD compared with the general pediatric population, primarily associated with an increased rate of gastrointestinal cancers,” wrote senior author Tine Jess, MD, DMSci, Aalborg University, Copenhagen, and colleagues.
The study was published online March 1 in JAMA Network Open.
Previous research indicates that IBD is associated with an increased risk for colon, small bowel, and other types of cancer in adults, but the risk among children with IBD is not well understood.
In the current analysis, Dr. Jess and colleagues examined five population-based studies from North America and Europe, which included more than 19,800 participants with pediatric-onset IBD. Of these participants, 715 were later diagnosed with cancer.
Overall, the risk for cancer among individuals with pediatric-onset IBD was 2.4-fold higher than that of their peers without IBD, but those rates varied by IBD subtype. Those with Crohn’s disease, for instance, were about two times more likely to develop cancer, while those with ulcerative colitis were 2.6 times more likely to develop cancer later.
Two studies included in the meta-analysis broke down results by sex and found that the risk for cancer was higher among male versus female patients (pooled relative rates [pRR], 3.23 in men and 2.45 in women).
These two studies also calculated the risk for cancer by exposure to thiopurines. Patients receiving these immunosuppressive drugs had an increased relative rate of cancer (pRR, 2.09). Although numerically higher, this rate was not statistically higher compared with patients not exposed to the drugs (pRR, 1.82).
When looking at risk by cancer site, the authors consistently observed the highest relative rates for gastrointestinal cancers. Specifically, the investigators calculated a 55-fold increased risk for liver cancer (pRR, 55.4), followed by a 20-fold increased risk for colorectal cancer (pRR, 20.2), and a 16-fold increased risk for small bowel cancer (pRR, 16.2).
Despite such high estimates for gastrointestinal cancers, “this risk corresponds to a mean incidence rate of 0.3 cases of liver cancer, 0.6 cases of colorectal cancer, and 0.1 cases of small bowel cancer per 1,000 person-years in this population,” the authors noted.
In other words, “the overall incidence rate of cancer in this population is low,” at less than 3.3 cases per 1,000 person-years, the authors concluded.
Relative rates of extraintestinal cancers were even lower, with the highest risks for nonmelanoma skin cancer (pRR, 3.62), lymphoid cancer (pRR, 3.10), and melanoma (pRR, 2.05).
The authors suggest that identifying variables that might reduce cancer risk in pediatric patients who develop IBD could better shape management and prevention strategies.
CRC screening guidelines already recommend that children undergo a colonoscopy 6-8 years after being diagnosed with colitis extending beyond the rectum. Annual colonoscopy is also recommended for patients with primary sclerosing cholangitis from the time of diagnosis and annual screening for skin cancer is recommended for all patients with IBD.
The investigators further suggest that because ongoing inflammation is an important risk factor for cancer, early and adequate control of inflammation could be critical in the prevention of long-term complications.
The study was supported by a grant from the Danish National Research Foundation. Dr. Jess and coauthors Rahma Elmahdi, MD, Camilla Lemser, and Kristine Allin, MD, reported receiving grants from the Danish National Research Foundation National Center of Excellence during the conduct of the study. Coauthor Manasi Agrawal, MD, reported receiving grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK
Dupilumab shows histological and clinical benefit in larger eosinophilic esophagitis cohort
The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.
EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.
Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.
Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)
Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.
Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group.
Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.
On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).
“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.
Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.
In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”
LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.
A version of this article first appeared on Medscape.com.
The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.
EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.
Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.
Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)
Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.
Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group.
Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.
On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).
“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.
Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.
In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”
LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.
A version of this article first appeared on Medscape.com.
The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.
EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.
Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.
Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)
Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.
Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group.
Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.
On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).
“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.
Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.
In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”
LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.
A version of this article first appeared on Medscape.com.
REPORTING FROM AAAAI