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FDA warns about anaphylaxis after false-negative allergen tests
The Food and Drug Administration has issued a warning about the potential for patients to experience anaphylactic reactions after a negative skin test with any allergenic extract used to diagnose food allergies.
The FDA is requiring that an anaphylaxis warning after false-negative food allergen skin test results be added to the labels of these products in light of reports to the FDA’s Adverse Event Reporting System (FAERS), according to a March 3 statement.
The action follows the recognition of an increase in adverse event reports of false-negative test results with specific lots of “ALK-Abello’s Allergenic Extract-Peanut (Arachis hypogaea) – For Diagnostic Use Only.” Some of these reports “were associated with life-threatening anaphylaxis from subsequent exposure to peanut,” according to the statement. “FDA determined that the risk of anaphylaxis following false-negative food allergen skin test results is applicable to all allergenic extracts for the diagnosis of food allergies,” the statement notes.
To date, four lots of allergenic extracts have been voluntarily withdrawn from the market by the manufacturer, in November and December 2022, and should not be used.
Although some allergenic extracts are standardized, those used in the diagnosis of food allergy currently licensed by the FDA for use in the United States are nonstandardized, so potency may vary by lot.
The FDA advises health care professionals to consider confirming a negative skin test with serologic testing for peanut-specific IgE or conducting a medically supervised oral food challenge in patients, “based on the patient’s clinical history and the index of suspicion.”
The FDA also urges patients to discuss negative food allergen skin test results with their health care providers to determine the possible need for additional testing and to review the symptoms of a severe allergic reaction.
Any adverse events or side effects associated with allergenic products should be reported to the FDA via the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has issued a warning about the potential for patients to experience anaphylactic reactions after a negative skin test with any allergenic extract used to diagnose food allergies.
The FDA is requiring that an anaphylaxis warning after false-negative food allergen skin test results be added to the labels of these products in light of reports to the FDA’s Adverse Event Reporting System (FAERS), according to a March 3 statement.
The action follows the recognition of an increase in adverse event reports of false-negative test results with specific lots of “ALK-Abello’s Allergenic Extract-Peanut (Arachis hypogaea) – For Diagnostic Use Only.” Some of these reports “were associated with life-threatening anaphylaxis from subsequent exposure to peanut,” according to the statement. “FDA determined that the risk of anaphylaxis following false-negative food allergen skin test results is applicable to all allergenic extracts for the diagnosis of food allergies,” the statement notes.
To date, four lots of allergenic extracts have been voluntarily withdrawn from the market by the manufacturer, in November and December 2022, and should not be used.
Although some allergenic extracts are standardized, those used in the diagnosis of food allergy currently licensed by the FDA for use in the United States are nonstandardized, so potency may vary by lot.
The FDA advises health care professionals to consider confirming a negative skin test with serologic testing for peanut-specific IgE or conducting a medically supervised oral food challenge in patients, “based on the patient’s clinical history and the index of suspicion.”
The FDA also urges patients to discuss negative food allergen skin test results with their health care providers to determine the possible need for additional testing and to review the symptoms of a severe allergic reaction.
Any adverse events or side effects associated with allergenic products should be reported to the FDA via the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has issued a warning about the potential for patients to experience anaphylactic reactions after a negative skin test with any allergenic extract used to diagnose food allergies.
The FDA is requiring that an anaphylaxis warning after false-negative food allergen skin test results be added to the labels of these products in light of reports to the FDA’s Adverse Event Reporting System (FAERS), according to a March 3 statement.
The action follows the recognition of an increase in adverse event reports of false-negative test results with specific lots of “ALK-Abello’s Allergenic Extract-Peanut (Arachis hypogaea) – For Diagnostic Use Only.” Some of these reports “were associated with life-threatening anaphylaxis from subsequent exposure to peanut,” according to the statement. “FDA determined that the risk of anaphylaxis following false-negative food allergen skin test results is applicable to all allergenic extracts for the diagnosis of food allergies,” the statement notes.
To date, four lots of allergenic extracts have been voluntarily withdrawn from the market by the manufacturer, in November and December 2022, and should not be used.
Although some allergenic extracts are standardized, those used in the diagnosis of food allergy currently licensed by the FDA for use in the United States are nonstandardized, so potency may vary by lot.
The FDA advises health care professionals to consider confirming a negative skin test with serologic testing for peanut-specific IgE or conducting a medically supervised oral food challenge in patients, “based on the patient’s clinical history and the index of suspicion.”
The FDA also urges patients to discuss negative food allergen skin test results with their health care providers to determine the possible need for additional testing and to review the symptoms of a severe allergic reaction.
Any adverse events or side effects associated with allergenic products should be reported to the FDA via the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
A version of this article first appeared on Medscape.com.
A 9-year-old male presents with multiple thick scaly plaques on scalp, ears, and trunk
Given the characteristic clinical presentation, the most likely diagnosis is psoriasis.
Psoriasis is a chronic immune-mediated disease that is characterized by well-demarcated thick scaly plaques on face, scalp, and intertriginous skin. Psoriasis is more common in adults than children, but the incidence of psoriasis in children has increased over time.1 Clinical presentation of psoriasis includes erythematous hyperkeratotic plaques, usually sharply demarcated. Pediatric patients may have multiple small papules and plaques less than 1 cm in size – “drop-size” – known as guttate lesions. Scalp and facial involvement are common in children. Chronic, inflamed plaques with coarse scale can involve ears, elbows, knees, and umbilicus, and nail changes can include pits, ridges, hyperkeratosis, and onycholysis or “oil spots.” While the diagnosis is clinical, biopsy can sometimes be useful to distinguish psoriasis from other papulosquamous conditions. Psoriasis in children is associated with obesity, higher rates of cardiovascular disease over a lifetime, as well as arthritis and mental health disorders.2
What’s the differential diagnosis?
The differential diagnosis for psoriasis can include papulosquamous diseases such as nummular eczema, pityriasis rosea, and pityriasis rubra pilaris. Tinea corporis may also be considered.
Nummular eczema, also known as “discoid eczema” is characterized by multiple pruritic, coin-shaped, eczematous lesions that may be actively oozing. The term “nummular” is derived from the Latin for “coin,” as lesions are distinct and annular. It is commonly associated with atopic dermatitis, and may be seen with contact dermatitis as well. Oozing, lichenification, hyperpigmentation and limited extent of skin coverage can help distinguish nummular dermatitis from psoriasis.
Pityriasis rosea is a common self-limited disease that is characterized by the appearance of acute, oval, papulosquamous patches on the trunk and proximal areas of the extremities. It usually begins with a characteristic “herald” patch, a single round or oval, sharply demarcated, pink lesion on the chest, neck, or back. Pityriasis rosea and guttate psoriasis may show similar clinical findings but the latter lacks a herald patch and is often preceded by streptococcal throat infection.
Pityriasis rubra pilaris is a rarer inflammatory disease characterized by follicular, hyperkeratotic papules, thick orange waxy palms (palmoplantar keratoderma), and erythroderma. It can also cause hair loss, nail changes, and itching. The rash shows areas with no involvement, “islands of sparing,” which is a signature characteristic of pityriasis rubra pilaris. Skin biopsies are an important diagnostic tool for pityriasis rubra pilaris. In the case of circumscribed pityriasis rubra pilaris, it may look similar to psoriasis, but it can be differentiated in that it is often accompanied by characteristic follicular papules and involvement of the palms, which are more waxy and orange in color.
When evaluating annular scaly patches, it is always important to consider tinea corporis. Tinea corporis will commonly have an annular border of scale with relative clearing in the center of lesions. In addition, when topical corticosteroids are used for prolonged periods, skin fungal infections can develop into “tinea incognito,” with paradoxical worsening since the immune response is suppressed and the fungal infection worsens.
Our patient had been previously treated with topical corticosteroids (medium to high strength) and topical calcineurin inhibitors without significant improvement. Other topical therapies for psoriasis include vitamin analogues, tazarotene, and newer therapies such as topical roflumilast (a phosphodiesterase-4 inhibitor approved for psoriasis in children over 12 years of age).3,4 In addition, as the indications for biological agents have been expanded, there are various options for treating psoriasis in children and adolescents when more active treatment is needed. Systemic therapies for more severe disease include traditional systemic immunosuppressives (for example, methotrexate, cyclosporine) and biologic agents. The four biologic agents currently approved for children are etanercept, ustekinumab, ixekizumab, and secukinumab. Our patient was treated with ustekinumab, which is an injectable biologic agent that blocks interleukin-12/23, with good response to date.
Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology; Dr. Choi is a visiting research physician in the division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice-chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California, San Diego, and Rady Children’s Hospital, San Diego. They have no relevant disclosures.
References
1. Tollefson MM et al. J Am Acad Dermatol. 2010;62(6):979-87.
2. Menter A et al. J Am Acad Dermatol. 2020;82(1):161-201.
3. Mark G et al. JAMA. 2022;328(11):1073-84.
4. Eichenfield LF et al. Pediatr Dermatol. 2018;35(2):170-81.
Given the characteristic clinical presentation, the most likely diagnosis is psoriasis.
Psoriasis is a chronic immune-mediated disease that is characterized by well-demarcated thick scaly plaques on face, scalp, and intertriginous skin. Psoriasis is more common in adults than children, but the incidence of psoriasis in children has increased over time.1 Clinical presentation of psoriasis includes erythematous hyperkeratotic plaques, usually sharply demarcated. Pediatric patients may have multiple small papules and plaques less than 1 cm in size – “drop-size” – known as guttate lesions. Scalp and facial involvement are common in children. Chronic, inflamed plaques with coarse scale can involve ears, elbows, knees, and umbilicus, and nail changes can include pits, ridges, hyperkeratosis, and onycholysis or “oil spots.” While the diagnosis is clinical, biopsy can sometimes be useful to distinguish psoriasis from other papulosquamous conditions. Psoriasis in children is associated with obesity, higher rates of cardiovascular disease over a lifetime, as well as arthritis and mental health disorders.2
What’s the differential diagnosis?
The differential diagnosis for psoriasis can include papulosquamous diseases such as nummular eczema, pityriasis rosea, and pityriasis rubra pilaris. Tinea corporis may also be considered.
Nummular eczema, also known as “discoid eczema” is characterized by multiple pruritic, coin-shaped, eczematous lesions that may be actively oozing. The term “nummular” is derived from the Latin for “coin,” as lesions are distinct and annular. It is commonly associated with atopic dermatitis, and may be seen with contact dermatitis as well. Oozing, lichenification, hyperpigmentation and limited extent of skin coverage can help distinguish nummular dermatitis from psoriasis.
Pityriasis rosea is a common self-limited disease that is characterized by the appearance of acute, oval, papulosquamous patches on the trunk and proximal areas of the extremities. It usually begins with a characteristic “herald” patch, a single round or oval, sharply demarcated, pink lesion on the chest, neck, or back. Pityriasis rosea and guttate psoriasis may show similar clinical findings but the latter lacks a herald patch and is often preceded by streptococcal throat infection.
Pityriasis rubra pilaris is a rarer inflammatory disease characterized by follicular, hyperkeratotic papules, thick orange waxy palms (palmoplantar keratoderma), and erythroderma. It can also cause hair loss, nail changes, and itching. The rash shows areas with no involvement, “islands of sparing,” which is a signature characteristic of pityriasis rubra pilaris. Skin biopsies are an important diagnostic tool for pityriasis rubra pilaris. In the case of circumscribed pityriasis rubra pilaris, it may look similar to psoriasis, but it can be differentiated in that it is often accompanied by characteristic follicular papules and involvement of the palms, which are more waxy and orange in color.
When evaluating annular scaly patches, it is always important to consider tinea corporis. Tinea corporis will commonly have an annular border of scale with relative clearing in the center of lesions. In addition, when topical corticosteroids are used for prolonged periods, skin fungal infections can develop into “tinea incognito,” with paradoxical worsening since the immune response is suppressed and the fungal infection worsens.
Our patient had been previously treated with topical corticosteroids (medium to high strength) and topical calcineurin inhibitors without significant improvement. Other topical therapies for psoriasis include vitamin analogues, tazarotene, and newer therapies such as topical roflumilast (a phosphodiesterase-4 inhibitor approved for psoriasis in children over 12 years of age).3,4 In addition, as the indications for biological agents have been expanded, there are various options for treating psoriasis in children and adolescents when more active treatment is needed. Systemic therapies for more severe disease include traditional systemic immunosuppressives (for example, methotrexate, cyclosporine) and biologic agents. The four biologic agents currently approved for children are etanercept, ustekinumab, ixekizumab, and secukinumab. Our patient was treated with ustekinumab, which is an injectable biologic agent that blocks interleukin-12/23, with good response to date.
Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology; Dr. Choi is a visiting research physician in the division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice-chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California, San Diego, and Rady Children’s Hospital, San Diego. They have no relevant disclosures.
References
1. Tollefson MM et al. J Am Acad Dermatol. 2010;62(6):979-87.
2. Menter A et al. J Am Acad Dermatol. 2020;82(1):161-201.
3. Mark G et al. JAMA. 2022;328(11):1073-84.
4. Eichenfield LF et al. Pediatr Dermatol. 2018;35(2):170-81.
Given the characteristic clinical presentation, the most likely diagnosis is psoriasis.
Psoriasis is a chronic immune-mediated disease that is characterized by well-demarcated thick scaly plaques on face, scalp, and intertriginous skin. Psoriasis is more common in adults than children, but the incidence of psoriasis in children has increased over time.1 Clinical presentation of psoriasis includes erythematous hyperkeratotic plaques, usually sharply demarcated. Pediatric patients may have multiple small papules and plaques less than 1 cm in size – “drop-size” – known as guttate lesions. Scalp and facial involvement are common in children. Chronic, inflamed plaques with coarse scale can involve ears, elbows, knees, and umbilicus, and nail changes can include pits, ridges, hyperkeratosis, and onycholysis or “oil spots.” While the diagnosis is clinical, biopsy can sometimes be useful to distinguish psoriasis from other papulosquamous conditions. Psoriasis in children is associated with obesity, higher rates of cardiovascular disease over a lifetime, as well as arthritis and mental health disorders.2
What’s the differential diagnosis?
The differential diagnosis for psoriasis can include papulosquamous diseases such as nummular eczema, pityriasis rosea, and pityriasis rubra pilaris. Tinea corporis may also be considered.
Nummular eczema, also known as “discoid eczema” is characterized by multiple pruritic, coin-shaped, eczematous lesions that may be actively oozing. The term “nummular” is derived from the Latin for “coin,” as lesions are distinct and annular. It is commonly associated with atopic dermatitis, and may be seen with contact dermatitis as well. Oozing, lichenification, hyperpigmentation and limited extent of skin coverage can help distinguish nummular dermatitis from psoriasis.
Pityriasis rosea is a common self-limited disease that is characterized by the appearance of acute, oval, papulosquamous patches on the trunk and proximal areas of the extremities. It usually begins with a characteristic “herald” patch, a single round or oval, sharply demarcated, pink lesion on the chest, neck, or back. Pityriasis rosea and guttate psoriasis may show similar clinical findings but the latter lacks a herald patch and is often preceded by streptococcal throat infection.
Pityriasis rubra pilaris is a rarer inflammatory disease characterized by follicular, hyperkeratotic papules, thick orange waxy palms (palmoplantar keratoderma), and erythroderma. It can also cause hair loss, nail changes, and itching. The rash shows areas with no involvement, “islands of sparing,” which is a signature characteristic of pityriasis rubra pilaris. Skin biopsies are an important diagnostic tool for pityriasis rubra pilaris. In the case of circumscribed pityriasis rubra pilaris, it may look similar to psoriasis, but it can be differentiated in that it is often accompanied by characteristic follicular papules and involvement of the palms, which are more waxy and orange in color.
When evaluating annular scaly patches, it is always important to consider tinea corporis. Tinea corporis will commonly have an annular border of scale with relative clearing in the center of lesions. In addition, when topical corticosteroids are used for prolonged periods, skin fungal infections can develop into “tinea incognito,” with paradoxical worsening since the immune response is suppressed and the fungal infection worsens.
Our patient had been previously treated with topical corticosteroids (medium to high strength) and topical calcineurin inhibitors without significant improvement. Other topical therapies for psoriasis include vitamin analogues, tazarotene, and newer therapies such as topical roflumilast (a phosphodiesterase-4 inhibitor approved for psoriasis in children over 12 years of age).3,4 In addition, as the indications for biological agents have been expanded, there are various options for treating psoriasis in children and adolescents when more active treatment is needed. Systemic therapies for more severe disease include traditional systemic immunosuppressives (for example, methotrexate, cyclosporine) and biologic agents. The four biologic agents currently approved for children are etanercept, ustekinumab, ixekizumab, and secukinumab. Our patient was treated with ustekinumab, which is an injectable biologic agent that blocks interleukin-12/23, with good response to date.
Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology; Dr. Choi is a visiting research physician in the division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice-chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California, San Diego, and Rady Children’s Hospital, San Diego. They have no relevant disclosures.
References
1. Tollefson MM et al. J Am Acad Dermatol. 2010;62(6):979-87.
2. Menter A et al. J Am Acad Dermatol. 2020;82(1):161-201.
3. Mark G et al. JAMA. 2022;328(11):1073-84.
4. Eichenfield LF et al. Pediatr Dermatol. 2018;35(2):170-81.
A 9-year-old male is seen in the clinic with a 1-year history of multiple thick scaly plaques on scalp, ears, and trunk. He has been treated with hydrocortisone 1% ointment with no change in the lesions. He had upper respiratory tract symptoms 3 weeks prior to the visit.
Examination reveals erythematous, well-demarcated plaques of the anterior scalp with thick overlying micaceous scale with some extension onto the forehead and temples. Additionally, erythematous scaly patches on the ear, axilla, and umbilicus were noted. There was no palmar or plantar involvement. He denied joint swelling, stiffness, or pain in the morning.
Induced labor associated with poor school performance of offspring
On average, children born following induced labor perform worse at school at age 12 years than their peers who were born after spontaneous onset of labor. This is the outcome of a report by Anita Ravelli, PhD, and her team of Dutch researchers in the department of obstetrics and gynecology of the Amsterdam University Medical Center, published in Acta Obstetricia et Gynecologica Scandinavica.
For the retrospective cohort study, the team analyzed data from almost 230,000 patients. According to these data, the likelihood of children reaching higher secondary school level is around 10% lower after elective induction of labor.
Labor induction frequent
These days in Germany, more than 20% of all births are induced. Sometimes this decision is made because of medical reasons, such as the woman’s having gestational diabetes, the presence of gestational toxicity, or the occurrence of a premature rupture of membranes. However, contractions are most often artificially triggered because the expected delivery date has passed.
Guidelines from the German Society of Gynecology and Obstetrics recommend inducing labor if there is a medical indication and if more than 10 days have passed since the expected delivery date. After 14 days, induction is strongly advised. This recommendation is based on studies that indicate that the child is at increased risk of disease and death once the expected delivery date is far exceeded.
Causal relationship unproven
It is still unclear whether and to what extent inducing labor affects a child’s neurologic development. Since the frequency of induced labor has increased greatly worldwide, Dr. Ravelli and her colleagues investigated this matter.
The study may have limited validity, however. “The outcome of the study only determines an association between spontaneous labor in mature children versus induced labor and a school performance test at 12 years of age,” said Maria Delius, MD, MPH, head of the Perinatal Center at the Clinic and Polyclinic for Obstetrics and Gynecology of the Ludwig Maximilian University of Munich. “The study is unable to prove any causality, even if it sounds that way in the abstract.”
This publication may in no way instigate a change in current practices, Dr. Delius emphasized. “There is a lot of potential for the wrong conclusions to be drawn from this study, and as a result – if it is presented and perceived in a subjective manner in public – to also cause harm to mothers and children,” she warned. The study also must not be associated with the drug misoprostol, since the various mechanical and medicinal methods of induction were not the topic of the Dutch investigation.
Gestational-week differences
The primary author of the study, Renee J. Burger, MD, PhD, of Dr. Ravelli’s UMC team, and her colleagues assessed the school performance of 226,684 children at age 12 years who were born in the 37th to 42nd week of gestation (WOG) between 2003 and 2008 in the Netherlands following an uncomplicated single pregnancy. They compared school performance, divided for each of the six WOG analyzed, between children whose birth was mechanically or medicinally induced and those who were born without intervention.
According to the report by the researchers, induced labor at every WOG up to the 41st week was associated with lower school performance in the children, compared with a spontaneous birth. In addition, fewer children whose birth was induced reached a higher secondary level of education. After 38 WOG, the figure stood at 48%, compared with 54% of children who were born without intervention. For 12-year-olds not born until the 42nd WOG, there were no significant differences between the two groups investigated.
Prospective studies pending
Dr. Burger and Dr. Ravelli emphasized that the results do not indicate that every child born after an induced labor will perform worse at school. This is a statistical correlation that cannot be transferred to a case-by-case basis. In addition, it is unlikely that all disruptive factors could be taken into consideration during the analyses. Nonetheless, the researchers conclude that the long-term effects of inducing labor should be considered during consultation and decision-making in the future.
In general, it is important that future randomized, controlled studies incorporate long-term measurements in their results and conclusions so that complete data on the present topic can be gathered. “Although the effect on the individual child is likely subtle, the impact on society due to the large number of early-term labor inductions should not be underestimated,” the authors wrote.
Unexamined disruptive factors
Sven Kehl, MD, PhD, senior physician of the department of obstetrics and gynecology and coordinator of the University Perinatal Center of Franconia at the University Hospital of Erlangen, Germany, is of a similar opinion. “Inducing labor causes birth to occur sooner and therefore for the pregnancy to finish prematurely,” said Dr. Kehl. Such premature births, not the mechanical or medicinal procedures for inducing labor, could affect the child’s cerebral development. “The results of this study suggest that inducing labor in uncomplicated pregnancies, in which there are no relevant medical indications, should be avoided,” said Dr. Kehl. In these cases, the mother should wait for a natural birth.
Some of the study’s strengths include the large quantity of data, the large number of participants, and the various disruptive factors taken into consideration, such as the mother’s level of education, according to Dr. Kehl. “But it is not a study from which causality can be derived,” he said.
Not all the potential disruptive factors could be found in the available data. For example, information regarding familial status, the father’s level of education, the parents’ smoking status, or the mother’s body mass index was missing. Also, only a small number of the possible indications for inducing labor was disclosed.
No elective inductions
The study is unlikely to have a major effect on practice in German maternity clinics, since the routine induction of labor from the 39th WOG has always been regarded critically in German-speaking countries, said Dr. Kehl. It is still true that if there are any risks, a risk-benefit analysis must be performed, and the risks to the mother or child must be evaluated when considering labor induction.
“If there are no medical reasons for inducing labor, the women must also be informed about the possible long-term consequences and not just about the short-term risks,” said Dr. Kehl.
His colleague in Berlin, Michael Abou-Dakn, MD, chief physician of gynecology and obstetrics at the St. Joseph’s Hospital, Berlin-Tempelhof, was more categorical. “It is right to criticize the fact that over 20% of births in Germany are induced,” he said. He is rather dubious, however, about the effects on school performance found in the study following induced labor. Still, the investigation is a reminder that inducing labor could involve side effects. “There should therefore be no elective inductions, or any without a clear indication,” said Dr. Abou-Dakn.
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
On average, children born following induced labor perform worse at school at age 12 years than their peers who were born after spontaneous onset of labor. This is the outcome of a report by Anita Ravelli, PhD, and her team of Dutch researchers in the department of obstetrics and gynecology of the Amsterdam University Medical Center, published in Acta Obstetricia et Gynecologica Scandinavica.
For the retrospective cohort study, the team analyzed data from almost 230,000 patients. According to these data, the likelihood of children reaching higher secondary school level is around 10% lower after elective induction of labor.
Labor induction frequent
These days in Germany, more than 20% of all births are induced. Sometimes this decision is made because of medical reasons, such as the woman’s having gestational diabetes, the presence of gestational toxicity, or the occurrence of a premature rupture of membranes. However, contractions are most often artificially triggered because the expected delivery date has passed.
Guidelines from the German Society of Gynecology and Obstetrics recommend inducing labor if there is a medical indication and if more than 10 days have passed since the expected delivery date. After 14 days, induction is strongly advised. This recommendation is based on studies that indicate that the child is at increased risk of disease and death once the expected delivery date is far exceeded.
Causal relationship unproven
It is still unclear whether and to what extent inducing labor affects a child’s neurologic development. Since the frequency of induced labor has increased greatly worldwide, Dr. Ravelli and her colleagues investigated this matter.
The study may have limited validity, however. “The outcome of the study only determines an association between spontaneous labor in mature children versus induced labor and a school performance test at 12 years of age,” said Maria Delius, MD, MPH, head of the Perinatal Center at the Clinic and Polyclinic for Obstetrics and Gynecology of the Ludwig Maximilian University of Munich. “The study is unable to prove any causality, even if it sounds that way in the abstract.”
This publication may in no way instigate a change in current practices, Dr. Delius emphasized. “There is a lot of potential for the wrong conclusions to be drawn from this study, and as a result – if it is presented and perceived in a subjective manner in public – to also cause harm to mothers and children,” she warned. The study also must not be associated with the drug misoprostol, since the various mechanical and medicinal methods of induction were not the topic of the Dutch investigation.
Gestational-week differences
The primary author of the study, Renee J. Burger, MD, PhD, of Dr. Ravelli’s UMC team, and her colleagues assessed the school performance of 226,684 children at age 12 years who were born in the 37th to 42nd week of gestation (WOG) between 2003 and 2008 in the Netherlands following an uncomplicated single pregnancy. They compared school performance, divided for each of the six WOG analyzed, between children whose birth was mechanically or medicinally induced and those who were born without intervention.
According to the report by the researchers, induced labor at every WOG up to the 41st week was associated with lower school performance in the children, compared with a spontaneous birth. In addition, fewer children whose birth was induced reached a higher secondary level of education. After 38 WOG, the figure stood at 48%, compared with 54% of children who were born without intervention. For 12-year-olds not born until the 42nd WOG, there were no significant differences between the two groups investigated.
Prospective studies pending
Dr. Burger and Dr. Ravelli emphasized that the results do not indicate that every child born after an induced labor will perform worse at school. This is a statistical correlation that cannot be transferred to a case-by-case basis. In addition, it is unlikely that all disruptive factors could be taken into consideration during the analyses. Nonetheless, the researchers conclude that the long-term effects of inducing labor should be considered during consultation and decision-making in the future.
In general, it is important that future randomized, controlled studies incorporate long-term measurements in their results and conclusions so that complete data on the present topic can be gathered. “Although the effect on the individual child is likely subtle, the impact on society due to the large number of early-term labor inductions should not be underestimated,” the authors wrote.
Unexamined disruptive factors
Sven Kehl, MD, PhD, senior physician of the department of obstetrics and gynecology and coordinator of the University Perinatal Center of Franconia at the University Hospital of Erlangen, Germany, is of a similar opinion. “Inducing labor causes birth to occur sooner and therefore for the pregnancy to finish prematurely,” said Dr. Kehl. Such premature births, not the mechanical or medicinal procedures for inducing labor, could affect the child’s cerebral development. “The results of this study suggest that inducing labor in uncomplicated pregnancies, in which there are no relevant medical indications, should be avoided,” said Dr. Kehl. In these cases, the mother should wait for a natural birth.
Some of the study’s strengths include the large quantity of data, the large number of participants, and the various disruptive factors taken into consideration, such as the mother’s level of education, according to Dr. Kehl. “But it is not a study from which causality can be derived,” he said.
Not all the potential disruptive factors could be found in the available data. For example, information regarding familial status, the father’s level of education, the parents’ smoking status, or the mother’s body mass index was missing. Also, only a small number of the possible indications for inducing labor was disclosed.
No elective inductions
The study is unlikely to have a major effect on practice in German maternity clinics, since the routine induction of labor from the 39th WOG has always been regarded critically in German-speaking countries, said Dr. Kehl. It is still true that if there are any risks, a risk-benefit analysis must be performed, and the risks to the mother or child must be evaluated when considering labor induction.
“If there are no medical reasons for inducing labor, the women must also be informed about the possible long-term consequences and not just about the short-term risks,” said Dr. Kehl.
His colleague in Berlin, Michael Abou-Dakn, MD, chief physician of gynecology and obstetrics at the St. Joseph’s Hospital, Berlin-Tempelhof, was more categorical. “It is right to criticize the fact that over 20% of births in Germany are induced,” he said. He is rather dubious, however, about the effects on school performance found in the study following induced labor. Still, the investigation is a reminder that inducing labor could involve side effects. “There should therefore be no elective inductions, or any without a clear indication,” said Dr. Abou-Dakn.
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
On average, children born following induced labor perform worse at school at age 12 years than their peers who were born after spontaneous onset of labor. This is the outcome of a report by Anita Ravelli, PhD, and her team of Dutch researchers in the department of obstetrics and gynecology of the Amsterdam University Medical Center, published in Acta Obstetricia et Gynecologica Scandinavica.
For the retrospective cohort study, the team analyzed data from almost 230,000 patients. According to these data, the likelihood of children reaching higher secondary school level is around 10% lower after elective induction of labor.
Labor induction frequent
These days in Germany, more than 20% of all births are induced. Sometimes this decision is made because of medical reasons, such as the woman’s having gestational diabetes, the presence of gestational toxicity, or the occurrence of a premature rupture of membranes. However, contractions are most often artificially triggered because the expected delivery date has passed.
Guidelines from the German Society of Gynecology and Obstetrics recommend inducing labor if there is a medical indication and if more than 10 days have passed since the expected delivery date. After 14 days, induction is strongly advised. This recommendation is based on studies that indicate that the child is at increased risk of disease and death once the expected delivery date is far exceeded.
Causal relationship unproven
It is still unclear whether and to what extent inducing labor affects a child’s neurologic development. Since the frequency of induced labor has increased greatly worldwide, Dr. Ravelli and her colleagues investigated this matter.
The study may have limited validity, however. “The outcome of the study only determines an association between spontaneous labor in mature children versus induced labor and a school performance test at 12 years of age,” said Maria Delius, MD, MPH, head of the Perinatal Center at the Clinic and Polyclinic for Obstetrics and Gynecology of the Ludwig Maximilian University of Munich. “The study is unable to prove any causality, even if it sounds that way in the abstract.”
This publication may in no way instigate a change in current practices, Dr. Delius emphasized. “There is a lot of potential for the wrong conclusions to be drawn from this study, and as a result – if it is presented and perceived in a subjective manner in public – to also cause harm to mothers and children,” she warned. The study also must not be associated with the drug misoprostol, since the various mechanical and medicinal methods of induction were not the topic of the Dutch investigation.
Gestational-week differences
The primary author of the study, Renee J. Burger, MD, PhD, of Dr. Ravelli’s UMC team, and her colleagues assessed the school performance of 226,684 children at age 12 years who were born in the 37th to 42nd week of gestation (WOG) between 2003 and 2008 in the Netherlands following an uncomplicated single pregnancy. They compared school performance, divided for each of the six WOG analyzed, between children whose birth was mechanically or medicinally induced and those who were born without intervention.
According to the report by the researchers, induced labor at every WOG up to the 41st week was associated with lower school performance in the children, compared with a spontaneous birth. In addition, fewer children whose birth was induced reached a higher secondary level of education. After 38 WOG, the figure stood at 48%, compared with 54% of children who were born without intervention. For 12-year-olds not born until the 42nd WOG, there were no significant differences between the two groups investigated.
Prospective studies pending
Dr. Burger and Dr. Ravelli emphasized that the results do not indicate that every child born after an induced labor will perform worse at school. This is a statistical correlation that cannot be transferred to a case-by-case basis. In addition, it is unlikely that all disruptive factors could be taken into consideration during the analyses. Nonetheless, the researchers conclude that the long-term effects of inducing labor should be considered during consultation and decision-making in the future.
In general, it is important that future randomized, controlled studies incorporate long-term measurements in their results and conclusions so that complete data on the present topic can be gathered. “Although the effect on the individual child is likely subtle, the impact on society due to the large number of early-term labor inductions should not be underestimated,” the authors wrote.
Unexamined disruptive factors
Sven Kehl, MD, PhD, senior physician of the department of obstetrics and gynecology and coordinator of the University Perinatal Center of Franconia at the University Hospital of Erlangen, Germany, is of a similar opinion. “Inducing labor causes birth to occur sooner and therefore for the pregnancy to finish prematurely,” said Dr. Kehl. Such premature births, not the mechanical or medicinal procedures for inducing labor, could affect the child’s cerebral development. “The results of this study suggest that inducing labor in uncomplicated pregnancies, in which there are no relevant medical indications, should be avoided,” said Dr. Kehl. In these cases, the mother should wait for a natural birth.
Some of the study’s strengths include the large quantity of data, the large number of participants, and the various disruptive factors taken into consideration, such as the mother’s level of education, according to Dr. Kehl. “But it is not a study from which causality can be derived,” he said.
Not all the potential disruptive factors could be found in the available data. For example, information regarding familial status, the father’s level of education, the parents’ smoking status, or the mother’s body mass index was missing. Also, only a small number of the possible indications for inducing labor was disclosed.
No elective inductions
The study is unlikely to have a major effect on practice in German maternity clinics, since the routine induction of labor from the 39th WOG has always been regarded critically in German-speaking countries, said Dr. Kehl. It is still true that if there are any risks, a risk-benefit analysis must be performed, and the risks to the mother or child must be evaluated when considering labor induction.
“If there are no medical reasons for inducing labor, the women must also be informed about the possible long-term consequences and not just about the short-term risks,” said Dr. Kehl.
His colleague in Berlin, Michael Abou-Dakn, MD, chief physician of gynecology and obstetrics at the St. Joseph’s Hospital, Berlin-Tempelhof, was more categorical. “It is right to criticize the fact that over 20% of births in Germany are induced,” he said. He is rather dubious, however, about the effects on school performance found in the study following induced labor. Still, the investigation is a reminder that inducing labor could involve side effects. “There should therefore be no elective inductions, or any without a clear indication,” said Dr. Abou-Dakn.
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
Once-daily stimulant for ADHD safe, effective at 1 year
A once-daily oral stimulant medication for treatment of attention-deficit/hyperactivity disorder in individuals aged 6 years or older is safe and effective after 1 year of treatment, new research shows.
Results from a phase 3, multicenter dose optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate (d-MPH), co-formulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
As reported by this news organization, Azstarys was approved by the U.S. Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial as well.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study due to a TEAE during the treatment phase.
Investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale-5 (ADHD-RS-5) score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported here are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos. Full disclosures are reported in the original article.
A version of this article first appeared on Medscape.com.
A once-daily oral stimulant medication for treatment of attention-deficit/hyperactivity disorder in individuals aged 6 years or older is safe and effective after 1 year of treatment, new research shows.
Results from a phase 3, multicenter dose optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate (d-MPH), co-formulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
As reported by this news organization, Azstarys was approved by the U.S. Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial as well.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study due to a TEAE during the treatment phase.
Investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale-5 (ADHD-RS-5) score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported here are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos. Full disclosures are reported in the original article.
A version of this article first appeared on Medscape.com.
A once-daily oral stimulant medication for treatment of attention-deficit/hyperactivity disorder in individuals aged 6 years or older is safe and effective after 1 year of treatment, new research shows.
Results from a phase 3, multicenter dose optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate (d-MPH), co-formulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
As reported by this news organization, Azstarys was approved by the U.S. Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial as well.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study due to a TEAE during the treatment phase.
Investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale-5 (ADHD-RS-5) score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported here are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos. Full disclosures are reported in the original article.
A version of this article first appeared on Medscape.com.
Once-daily stimulant for ADHD safe, effective at 1 year
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
In utero exposure to asthma medication not tied to risks of neurodevelopmental disorders
The drugs included in the study were leukotriene-receptor antagonists (LTRAs), which are often used to treat allergic airway diseases, including asthma and allergic rhinitis.
“Over the years, the U.S. Food and Drug Administration has monitored post-marketing data about the potential harm of neuropsychiatric events (NEs) associated with montelukast, the first type of LTRAs, and issued boxed warnings about serious mental health side effects for montelukast in 2020,” said corresponding author Tsung-Chieh Yao, MD, of Chang Gung Memorial Hospital, Taiwan, in an interview.
However, evidence of a link between NEs and LTRA use has been inconsistent, according to Dr. Yao and colleagues.
“To date, it remains totally unknown whether the exposure to LTRAs during pregnancy is associated with the risk of neuropsychiatric events in offspring,” said Dr. Yao.
To address this question, the researchers used data from National Health Insurance Research Database in Taiwan to identify pregnant women and their offspring from 2009 to 2019. The initial study population included 576,157 mother-offspring pairs, including 1,995 LTRA-exposed and 574,162 nonexposed children.
The women had a diagnosis of asthma or allergic rhinitis; multiple births and children with congenital malformations were excluded. LTRA exposure was defined as any dispensed prescription for LTRAs during pregnancy. Approximately two-thirds of the mothers were aged 30-40 years at the time of delivery.
The findings were published in a research letter in JAMA Network Open.
In the study population at large, the incidence of the three neurodevelopmental disorders ADHD, autism spectrum disorder (ASD), and Tourette syndrome was not significantly different between those children exposed to LTRAs and those not exposed to LTRAs in utero (1.25% vs. 1.32%; 3.31% vs. 4.36%; and 0.45% vs. 0.83%, respectively).
After propensity score matching, the study population included 1,988 LTRA-exposed children and 19,863 nonexposed children. In this group, no significant associations appeared between prenatal LTRA exposure and the risk of attention-deficit/hyperactivity disorder (adjusted hazard ratio, 1.03), autism spectrum disorder (AHR, 1.01), and Tourette syndrome (AHR, 0.63).
Neither duration nor cumulative dose of LTRA use during pregnancy showed an association with ADHD, ASD, or Tourette syndrome in offspring. Duration of LTRA use was categorized as shorter or longer periods of 1-4 weeks vs. more than 4 weeks; cumulative dose was categorized as 1-170 mg vs. 170 mg or higher.
The findings were limited by the lack of randomization, inability to detect long-term risk, and potential lack of generalizability to non-Asian populations, and more research is needed to replicate the results, the researchers noted. However, the current findings were strengthened by the large study population, and suggest that LTRA use in pregnancy does not present a significant risk for NEs in children, which should be reassuring to clinicians and patients, they concluded.
The current study is the first to use the whole of Taiwan population data and extends previous studies by examining the association between LTRA use during pregnancy and risk of neuropsychiatric events in offspring, Dr. Yao said in an interview. “The possibly surprising, but reassuring, finding is that prenatal LTRA exposure did not increase risk of ADHD, ASD, and Tourette syndrome in offspring,” he said.
“Clinicians prescribing LTRAs such as montelukast (Singulair and generics) to pregnant women with asthma or allergic rhinitis may be reassured by our findings,” Dr. Yao added. The results offer real-world evidence to help inform decision-making about the use of LTRAs during pregnancy, although additional research is needed to replicate the study findings in other populations, he said.
The study was supported by the National Health Research Institutes, Taiwan, the Ministry of Science and Technology of Taiwan, the National Science and Technology Council of Taiwan, and the Chang Gung Medical Foundation. The researchers had no financial conflicts to disclose.
The drugs included in the study were leukotriene-receptor antagonists (LTRAs), which are often used to treat allergic airway diseases, including asthma and allergic rhinitis.
“Over the years, the U.S. Food and Drug Administration has monitored post-marketing data about the potential harm of neuropsychiatric events (NEs) associated with montelukast, the first type of LTRAs, and issued boxed warnings about serious mental health side effects for montelukast in 2020,” said corresponding author Tsung-Chieh Yao, MD, of Chang Gung Memorial Hospital, Taiwan, in an interview.
However, evidence of a link between NEs and LTRA use has been inconsistent, according to Dr. Yao and colleagues.
“To date, it remains totally unknown whether the exposure to LTRAs during pregnancy is associated with the risk of neuropsychiatric events in offspring,” said Dr. Yao.
To address this question, the researchers used data from National Health Insurance Research Database in Taiwan to identify pregnant women and their offspring from 2009 to 2019. The initial study population included 576,157 mother-offspring pairs, including 1,995 LTRA-exposed and 574,162 nonexposed children.
The women had a diagnosis of asthma or allergic rhinitis; multiple births and children with congenital malformations were excluded. LTRA exposure was defined as any dispensed prescription for LTRAs during pregnancy. Approximately two-thirds of the mothers were aged 30-40 years at the time of delivery.
The findings were published in a research letter in JAMA Network Open.
In the study population at large, the incidence of the three neurodevelopmental disorders ADHD, autism spectrum disorder (ASD), and Tourette syndrome was not significantly different between those children exposed to LTRAs and those not exposed to LTRAs in utero (1.25% vs. 1.32%; 3.31% vs. 4.36%; and 0.45% vs. 0.83%, respectively).
After propensity score matching, the study population included 1,988 LTRA-exposed children and 19,863 nonexposed children. In this group, no significant associations appeared between prenatal LTRA exposure and the risk of attention-deficit/hyperactivity disorder (adjusted hazard ratio, 1.03), autism spectrum disorder (AHR, 1.01), and Tourette syndrome (AHR, 0.63).
Neither duration nor cumulative dose of LTRA use during pregnancy showed an association with ADHD, ASD, or Tourette syndrome in offspring. Duration of LTRA use was categorized as shorter or longer periods of 1-4 weeks vs. more than 4 weeks; cumulative dose was categorized as 1-170 mg vs. 170 mg or higher.
The findings were limited by the lack of randomization, inability to detect long-term risk, and potential lack of generalizability to non-Asian populations, and more research is needed to replicate the results, the researchers noted. However, the current findings were strengthened by the large study population, and suggest that LTRA use in pregnancy does not present a significant risk for NEs in children, which should be reassuring to clinicians and patients, they concluded.
The current study is the first to use the whole of Taiwan population data and extends previous studies by examining the association between LTRA use during pregnancy and risk of neuropsychiatric events in offspring, Dr. Yao said in an interview. “The possibly surprising, but reassuring, finding is that prenatal LTRA exposure did not increase risk of ADHD, ASD, and Tourette syndrome in offspring,” he said.
“Clinicians prescribing LTRAs such as montelukast (Singulair and generics) to pregnant women with asthma or allergic rhinitis may be reassured by our findings,” Dr. Yao added. The results offer real-world evidence to help inform decision-making about the use of LTRAs during pregnancy, although additional research is needed to replicate the study findings in other populations, he said.
The study was supported by the National Health Research Institutes, Taiwan, the Ministry of Science and Technology of Taiwan, the National Science and Technology Council of Taiwan, and the Chang Gung Medical Foundation. The researchers had no financial conflicts to disclose.
The drugs included in the study were leukotriene-receptor antagonists (LTRAs), which are often used to treat allergic airway diseases, including asthma and allergic rhinitis.
“Over the years, the U.S. Food and Drug Administration has monitored post-marketing data about the potential harm of neuropsychiatric events (NEs) associated with montelukast, the first type of LTRAs, and issued boxed warnings about serious mental health side effects for montelukast in 2020,” said corresponding author Tsung-Chieh Yao, MD, of Chang Gung Memorial Hospital, Taiwan, in an interview.
However, evidence of a link between NEs and LTRA use has been inconsistent, according to Dr. Yao and colleagues.
“To date, it remains totally unknown whether the exposure to LTRAs during pregnancy is associated with the risk of neuropsychiatric events in offspring,” said Dr. Yao.
To address this question, the researchers used data from National Health Insurance Research Database in Taiwan to identify pregnant women and their offspring from 2009 to 2019. The initial study population included 576,157 mother-offspring pairs, including 1,995 LTRA-exposed and 574,162 nonexposed children.
The women had a diagnosis of asthma or allergic rhinitis; multiple births and children with congenital malformations were excluded. LTRA exposure was defined as any dispensed prescription for LTRAs during pregnancy. Approximately two-thirds of the mothers were aged 30-40 years at the time of delivery.
The findings were published in a research letter in JAMA Network Open.
In the study population at large, the incidence of the three neurodevelopmental disorders ADHD, autism spectrum disorder (ASD), and Tourette syndrome was not significantly different between those children exposed to LTRAs and those not exposed to LTRAs in utero (1.25% vs. 1.32%; 3.31% vs. 4.36%; and 0.45% vs. 0.83%, respectively).
After propensity score matching, the study population included 1,988 LTRA-exposed children and 19,863 nonexposed children. In this group, no significant associations appeared between prenatal LTRA exposure and the risk of attention-deficit/hyperactivity disorder (adjusted hazard ratio, 1.03), autism spectrum disorder (AHR, 1.01), and Tourette syndrome (AHR, 0.63).
Neither duration nor cumulative dose of LTRA use during pregnancy showed an association with ADHD, ASD, or Tourette syndrome in offspring. Duration of LTRA use was categorized as shorter or longer periods of 1-4 weeks vs. more than 4 weeks; cumulative dose was categorized as 1-170 mg vs. 170 mg or higher.
The findings were limited by the lack of randomization, inability to detect long-term risk, and potential lack of generalizability to non-Asian populations, and more research is needed to replicate the results, the researchers noted. However, the current findings were strengthened by the large study population, and suggest that LTRA use in pregnancy does not present a significant risk for NEs in children, which should be reassuring to clinicians and patients, they concluded.
The current study is the first to use the whole of Taiwan population data and extends previous studies by examining the association between LTRA use during pregnancy and risk of neuropsychiatric events in offspring, Dr. Yao said in an interview. “The possibly surprising, but reassuring, finding is that prenatal LTRA exposure did not increase risk of ADHD, ASD, and Tourette syndrome in offspring,” he said.
“Clinicians prescribing LTRAs such as montelukast (Singulair and generics) to pregnant women with asthma or allergic rhinitis may be reassured by our findings,” Dr. Yao added. The results offer real-world evidence to help inform decision-making about the use of LTRAs during pregnancy, although additional research is needed to replicate the study findings in other populations, he said.
The study was supported by the National Health Research Institutes, Taiwan, the Ministry of Science and Technology of Taiwan, the National Science and Technology Council of Taiwan, and the Chang Gung Medical Foundation. The researchers had no financial conflicts to disclose.
FROM JAMA NETWORK OPEN
Migraine after concussion linked to worse outcomes
researchers have found.
“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”
Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.
Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.
The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.
Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.
Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.
The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.
Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.
The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.
Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.
“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”
Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.
“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.
The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
researchers have found.
“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”
Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.
Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.
The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.
Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.
Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.
The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.
Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.
The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.
Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.
“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”
Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.
“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.
The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
researchers have found.
“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”
Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.
Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.
The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.
Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.
Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.
The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.
Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.
The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.
Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.
“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”
Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.
“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.
The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Causal link found between childhood obesity and adult-onset diabetes
Childhood obesity is a risk factor for four of the five subtypes of adult-onset diabetes, emphasizing the importance of childhood weight control, according to a collaborative study from the Karolinska Institutet in Stockholm, the University of Bristol (England), and Sun Yat-Sen University in China.
“Our finding is that children who have a bigger body size than the average have increased risks of developing almost all subtypes of adult-onset diabetes, except for the mild age-related subtype,” lead author Yuxia Wei, a PhD student from the Karolinska Institutet, said in an interview. “This tells us that it is important to prevent overweight/obesity in children and important for pediatric patients to lose weight if they have already been overweight/obese,” she added, while acknowledging that the study did not examine whether childhood weight loss would prevent adult-onset diabetes.
The study, published online in Diabetologia, used Mendelian randomization (MR), with data from genome-wide association studies (GWAS) of childhood obesity and the five subtypes of adult-onset diabetes: latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). MR is “a rather new but commonly used and established technique that uses genetic information to study the causal link between an environmental risk factor and a disease, while accounting for the influence of other risk factors,” Ms. Wei explained.
To identify genetic variations associated with obesity, the study used statistics from a GWAS of 453,169 Europeans who self-reported body size at age 10 years in the UK Biobank study. After adjustment for sex, age at baseline, type of genotyping array, and month of birth, they identified 295 independent single nucleotide polymorphisms (SNPs) for childhood body size.
The researchers also used data from two GWAS of European adults with newly diagnosed diabetes, or without diabetes, to identify SNPs in 8,581 individuals with LADA, 3,937 with SIDD, 3,874 with SIRD, 4,118 with MOD, and 5,605 with MARD.
They then used MR to assess the association of genetically predicted childhood body size with the different diabetes subtypes.
The analysis showed that, with the exception of MARD, all other adult-onset diabetes subtypes were causally associated with childhood obesity, with odds ratio of 1.62 for LADA, 2.11 for SIDD, 2.76 for SIRD, and 7.30 for MOD. However, a genetic correlation between childhood obesity and adult-onset diabetes was found only for MOD, and no other subtypes. “The weak genetic correlation between childhood obesity and adult diabetes indicates that the genes promoting childhood adiposity are largely distinct from those promoting diabetes during adulthood,” noted the authors.
The findings indicate that “childhood body size and MOD may share some genetic mutations,” added Ms. Wei. “That is to say, some genes may affect childhood body size and MOD simultaneously.” But the shared genes do demonstrate the causal effect of childhood obesity on MOD, she explained. The causal effect is demonstrated through the MR analysis.
Additionally, they noted that while “the link between childhood body size and SIRD is expected, given the adverse effects of adiposity on insulin sensitivity ... the smaller OR for SIRD than for MOD suggests that non–obesity-related and/or nongenetic effects may be the main factors underlying the development of SIRD.” Asked for her theory on how childhood body size could affect diabetes subtypes characterized by autoimmunity (LADA) or impaired insulin secretion (SIDD), Ms. Wei speculated that “excess fat around the pancreas can affect insulin secretion and that impaired insulin secretion is also an important problem for LADA.”
Another theory is that it might be “metabolic memory,” suggested Jordi Merino, PhD, of the University of Copenhagen and Harvard University, Boston, who was not involved in the research. “Being exposed to obesity during childhood will tell the body to produce more insulin/aberrant immunity responses later in life.”
Dr. Merino said that, overall, the study’s findings “highlight the long and lasting effect of early-life adiposity and metabolic alterations on different forms of adult-onset diabetes,” adding that this is the first evidence “that childhood adiposity is not only linked to the more traditional diabetes subtype consequence of increased insulin resistance but also subtypes driven by autoimmunity or impaired insulin secretion.” He explained that genetics is “only part of the story” driving increased diabetes risk and “we do not know much about other factors interacting with genetics, but the results from this Mendelian randomization analysis suggest that childhood obesity is a causal factor for all adult-onset diabetes subtypes. Identifying causal factors instead of associative factors is critical to implement more targeted preventive and therapeutic strategies.”
He acknowledged, “There is a long path for these results to be eventually implemented in clinical practice, but they can support early weight control strategies for preventing different diabetes subtypes.”
The study was supported by the Swedish Research Council, Research Council for Health, Working Life and Welfare, and Novo Nordisk Foundation. Ms. Wei received a scholarship from the China Scholarship Council. One coauthor is an employee of GlaxoSmithKline. Dr. Merino reported no conflicts of interest.
Childhood obesity is a risk factor for four of the five subtypes of adult-onset diabetes, emphasizing the importance of childhood weight control, according to a collaborative study from the Karolinska Institutet in Stockholm, the University of Bristol (England), and Sun Yat-Sen University in China.
“Our finding is that children who have a bigger body size than the average have increased risks of developing almost all subtypes of adult-onset diabetes, except for the mild age-related subtype,” lead author Yuxia Wei, a PhD student from the Karolinska Institutet, said in an interview. “This tells us that it is important to prevent overweight/obesity in children and important for pediatric patients to lose weight if they have already been overweight/obese,” she added, while acknowledging that the study did not examine whether childhood weight loss would prevent adult-onset diabetes.
The study, published online in Diabetologia, used Mendelian randomization (MR), with data from genome-wide association studies (GWAS) of childhood obesity and the five subtypes of adult-onset diabetes: latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). MR is “a rather new but commonly used and established technique that uses genetic information to study the causal link between an environmental risk factor and a disease, while accounting for the influence of other risk factors,” Ms. Wei explained.
To identify genetic variations associated with obesity, the study used statistics from a GWAS of 453,169 Europeans who self-reported body size at age 10 years in the UK Biobank study. After adjustment for sex, age at baseline, type of genotyping array, and month of birth, they identified 295 independent single nucleotide polymorphisms (SNPs) for childhood body size.
The researchers also used data from two GWAS of European adults with newly diagnosed diabetes, or without diabetes, to identify SNPs in 8,581 individuals with LADA, 3,937 with SIDD, 3,874 with SIRD, 4,118 with MOD, and 5,605 with MARD.
They then used MR to assess the association of genetically predicted childhood body size with the different diabetes subtypes.
The analysis showed that, with the exception of MARD, all other adult-onset diabetes subtypes were causally associated with childhood obesity, with odds ratio of 1.62 for LADA, 2.11 for SIDD, 2.76 for SIRD, and 7.30 for MOD. However, a genetic correlation between childhood obesity and adult-onset diabetes was found only for MOD, and no other subtypes. “The weak genetic correlation between childhood obesity and adult diabetes indicates that the genes promoting childhood adiposity are largely distinct from those promoting diabetes during adulthood,” noted the authors.
The findings indicate that “childhood body size and MOD may share some genetic mutations,” added Ms. Wei. “That is to say, some genes may affect childhood body size and MOD simultaneously.” But the shared genes do demonstrate the causal effect of childhood obesity on MOD, she explained. The causal effect is demonstrated through the MR analysis.
Additionally, they noted that while “the link between childhood body size and SIRD is expected, given the adverse effects of adiposity on insulin sensitivity ... the smaller OR for SIRD than for MOD suggests that non–obesity-related and/or nongenetic effects may be the main factors underlying the development of SIRD.” Asked for her theory on how childhood body size could affect diabetes subtypes characterized by autoimmunity (LADA) or impaired insulin secretion (SIDD), Ms. Wei speculated that “excess fat around the pancreas can affect insulin secretion and that impaired insulin secretion is also an important problem for LADA.”
Another theory is that it might be “metabolic memory,” suggested Jordi Merino, PhD, of the University of Copenhagen and Harvard University, Boston, who was not involved in the research. “Being exposed to obesity during childhood will tell the body to produce more insulin/aberrant immunity responses later in life.”
Dr. Merino said that, overall, the study’s findings “highlight the long and lasting effect of early-life adiposity and metabolic alterations on different forms of adult-onset diabetes,” adding that this is the first evidence “that childhood adiposity is not only linked to the more traditional diabetes subtype consequence of increased insulin resistance but also subtypes driven by autoimmunity or impaired insulin secretion.” He explained that genetics is “only part of the story” driving increased diabetes risk and “we do not know much about other factors interacting with genetics, but the results from this Mendelian randomization analysis suggest that childhood obesity is a causal factor for all adult-onset diabetes subtypes. Identifying causal factors instead of associative factors is critical to implement more targeted preventive and therapeutic strategies.”
He acknowledged, “There is a long path for these results to be eventually implemented in clinical practice, but they can support early weight control strategies for preventing different diabetes subtypes.”
The study was supported by the Swedish Research Council, Research Council for Health, Working Life and Welfare, and Novo Nordisk Foundation. Ms. Wei received a scholarship from the China Scholarship Council. One coauthor is an employee of GlaxoSmithKline. Dr. Merino reported no conflicts of interest.
Childhood obesity is a risk factor for four of the five subtypes of adult-onset diabetes, emphasizing the importance of childhood weight control, according to a collaborative study from the Karolinska Institutet in Stockholm, the University of Bristol (England), and Sun Yat-Sen University in China.
“Our finding is that children who have a bigger body size than the average have increased risks of developing almost all subtypes of adult-onset diabetes, except for the mild age-related subtype,” lead author Yuxia Wei, a PhD student from the Karolinska Institutet, said in an interview. “This tells us that it is important to prevent overweight/obesity in children and important for pediatric patients to lose weight if they have already been overweight/obese,” she added, while acknowledging that the study did not examine whether childhood weight loss would prevent adult-onset diabetes.
The study, published online in Diabetologia, used Mendelian randomization (MR), with data from genome-wide association studies (GWAS) of childhood obesity and the five subtypes of adult-onset diabetes: latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). MR is “a rather new but commonly used and established technique that uses genetic information to study the causal link between an environmental risk factor and a disease, while accounting for the influence of other risk factors,” Ms. Wei explained.
To identify genetic variations associated with obesity, the study used statistics from a GWAS of 453,169 Europeans who self-reported body size at age 10 years in the UK Biobank study. After adjustment for sex, age at baseline, type of genotyping array, and month of birth, they identified 295 independent single nucleotide polymorphisms (SNPs) for childhood body size.
The researchers also used data from two GWAS of European adults with newly diagnosed diabetes, or without diabetes, to identify SNPs in 8,581 individuals with LADA, 3,937 with SIDD, 3,874 with SIRD, 4,118 with MOD, and 5,605 with MARD.
They then used MR to assess the association of genetically predicted childhood body size with the different diabetes subtypes.
The analysis showed that, with the exception of MARD, all other adult-onset diabetes subtypes were causally associated with childhood obesity, with odds ratio of 1.62 for LADA, 2.11 for SIDD, 2.76 for SIRD, and 7.30 for MOD. However, a genetic correlation between childhood obesity and adult-onset diabetes was found only for MOD, and no other subtypes. “The weak genetic correlation between childhood obesity and adult diabetes indicates that the genes promoting childhood adiposity are largely distinct from those promoting diabetes during adulthood,” noted the authors.
The findings indicate that “childhood body size and MOD may share some genetic mutations,” added Ms. Wei. “That is to say, some genes may affect childhood body size and MOD simultaneously.” But the shared genes do demonstrate the causal effect of childhood obesity on MOD, she explained. The causal effect is demonstrated through the MR analysis.
Additionally, they noted that while “the link between childhood body size and SIRD is expected, given the adverse effects of adiposity on insulin sensitivity ... the smaller OR for SIRD than for MOD suggests that non–obesity-related and/or nongenetic effects may be the main factors underlying the development of SIRD.” Asked for her theory on how childhood body size could affect diabetes subtypes characterized by autoimmunity (LADA) or impaired insulin secretion (SIDD), Ms. Wei speculated that “excess fat around the pancreas can affect insulin secretion and that impaired insulin secretion is also an important problem for LADA.”
Another theory is that it might be “metabolic memory,” suggested Jordi Merino, PhD, of the University of Copenhagen and Harvard University, Boston, who was not involved in the research. “Being exposed to obesity during childhood will tell the body to produce more insulin/aberrant immunity responses later in life.”
Dr. Merino said that, overall, the study’s findings “highlight the long and lasting effect of early-life adiposity and metabolic alterations on different forms of adult-onset diabetes,” adding that this is the first evidence “that childhood adiposity is not only linked to the more traditional diabetes subtype consequence of increased insulin resistance but also subtypes driven by autoimmunity or impaired insulin secretion.” He explained that genetics is “only part of the story” driving increased diabetes risk and “we do not know much about other factors interacting with genetics, but the results from this Mendelian randomization analysis suggest that childhood obesity is a causal factor for all adult-onset diabetes subtypes. Identifying causal factors instead of associative factors is critical to implement more targeted preventive and therapeutic strategies.”
He acknowledged, “There is a long path for these results to be eventually implemented in clinical practice, but they can support early weight control strategies for preventing different diabetes subtypes.”
The study was supported by the Swedish Research Council, Research Council for Health, Working Life and Welfare, and Novo Nordisk Foundation. Ms. Wei received a scholarship from the China Scholarship Council. One coauthor is an employee of GlaxoSmithKline. Dr. Merino reported no conflicts of interest.
FROM DIABETOLOGIA
Troubling trend as both diabetes types rise among U.S. youth
The incidence of type 1 and type 2 diabetes continues to rise among children and adolescents in the United States, new data from the SEARCH for Diabetes in Youth study show.
The SEARCH data demonstrate an increase in the youth population aged 0-19 diagnosed with type 1 or type 2 diabetes in five representative U.S. centers. Between 2002 and 2018, the annual incidence rose by about 2% per year for type 1 diabetes and 5% per year for type 2 diabetes. The rates of increase for both types were greater among non-White than White youth.
These increases “will result in an expanding population of young adults at risk of developing early complications of diabetes whose health care needs will exceed those of their peers,” write Lynne E. Wagenknecht, DrPH, of Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues in their article, recently published in The Lancet Diabetes & Endocrinology.
In an accompanying editorial, Jonathan E. Shaw, MD, and Dianna J. Magliano, PhD, both at the Baker Heart and Diabetes Institute, Melbourne, write that one of the most “concerning findings” was a 7%-9% annual increase in the incidence of type 2 diabetes among Hispanic, Asian, and Pacific Islander populations.
“This is a health care crisis in the making. ...Youth and young-adult-onset type 2 diabetes are growing problems leading to poor outcomes and to widening social inequality, adversely affecting a population that might already be disadvantaged. Better information about its natural history, prevention, and management is urgently needed,” they write.
Upward trends in both diabetes types
Overall, 18,169 children and adolescents with type 1 diabetes and 5,293 with type 2 diabetes were identified over the 17-year study period in SEARCH. After adjustment for age, sex, and race/ethnicity, there was a significant increase in type 1 diabetes incidence from 19.5 cases/100,000 population in 2002-2003 to 22.2/100,000 in 2017-2018, a 2.02% annual increase.
The upward trend was even greater for type 2 diabetes, from 9.0/100,000 in 2002-2003 to 17.9/100,000 in 2017-2018, a 5.31% annual increase.
The annual rate of increase in type 1 diabetes was highest among Asian/Pacific Islander youth (4.84%), followed by Hispanic (4.14%) and Black youth (2.93%): All significantly rose over the 17 years.
For type 2 diabetes, significant annual rates of increase were also highest for Asian/Pacific Islanders (8.92%), followed by Hispanic (7.17%) and Black youth (5.99%).
Among youth aged 15-19 years, the overall incidence of type 2 diabetes exceeded that of type 1 diabetes (19.7 vs. 14.6/100,000).
The incidence of type 2 diabetes may be rising because of increased rates of obesity, as well as increased screening of at-risk youth, the authors say.
And, the editorialists note, obesity is also a risk factor for type 1 diabetes.
Peak incidence of type 1 diabetes occurred at age 10 years, while for type 2 diabetes, the peak was at 16 years. There were also seasonal peaks, occurring in January for type 1 diabetes and in August for type 2 diabetes. Those seasonal patterns have been previously reported; they are possibly because of increased viral infections and decreased sun exposure for the former, and increased physical exams in preparation for school in the latter, the authors speculate.
Dr. Shaw and Dr. Magliano note that the reduced incidence after age 16 years “might simply reflect a failure to diagnose,” suggesting that there will likely be an upturn in incidence in the subsequent decade.
The editorialists also point out: “Not only does the long duration of diabetes that youth-onset leads to cause a large burden of fatal and nonfatal complications, but it magnifies intergenerational effects.”
“When type 2 diabetes is already present before pregnancy, birth outcomes are worse, and the long-term metabolic health of the offspring is adversely affected. This does not bode well for the epidemic of diabetes and its complications.”
The study was funded by the Centers for Disease Control and Prevention and National Institutes of Health. The authors and Dr. Magliano have reported no relevant financial relationships. Dr. Shaw has reported receiving honoraria for lectures and for advisory boards and grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, Sanofi, Roche, Mylan, and Zuellig Pharma.
A version of this article originally appeared on Medscape.com.
The incidence of type 1 and type 2 diabetes continues to rise among children and adolescents in the United States, new data from the SEARCH for Diabetes in Youth study show.
The SEARCH data demonstrate an increase in the youth population aged 0-19 diagnosed with type 1 or type 2 diabetes in five representative U.S. centers. Between 2002 and 2018, the annual incidence rose by about 2% per year for type 1 diabetes and 5% per year for type 2 diabetes. The rates of increase for both types were greater among non-White than White youth.
These increases “will result in an expanding population of young adults at risk of developing early complications of diabetes whose health care needs will exceed those of their peers,” write Lynne E. Wagenknecht, DrPH, of Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues in their article, recently published in The Lancet Diabetes & Endocrinology.
In an accompanying editorial, Jonathan E. Shaw, MD, and Dianna J. Magliano, PhD, both at the Baker Heart and Diabetes Institute, Melbourne, write that one of the most “concerning findings” was a 7%-9% annual increase in the incidence of type 2 diabetes among Hispanic, Asian, and Pacific Islander populations.
“This is a health care crisis in the making. ...Youth and young-adult-onset type 2 diabetes are growing problems leading to poor outcomes and to widening social inequality, adversely affecting a population that might already be disadvantaged. Better information about its natural history, prevention, and management is urgently needed,” they write.
Upward trends in both diabetes types
Overall, 18,169 children and adolescents with type 1 diabetes and 5,293 with type 2 diabetes were identified over the 17-year study period in SEARCH. After adjustment for age, sex, and race/ethnicity, there was a significant increase in type 1 diabetes incidence from 19.5 cases/100,000 population in 2002-2003 to 22.2/100,000 in 2017-2018, a 2.02% annual increase.
The upward trend was even greater for type 2 diabetes, from 9.0/100,000 in 2002-2003 to 17.9/100,000 in 2017-2018, a 5.31% annual increase.
The annual rate of increase in type 1 diabetes was highest among Asian/Pacific Islander youth (4.84%), followed by Hispanic (4.14%) and Black youth (2.93%): All significantly rose over the 17 years.
For type 2 diabetes, significant annual rates of increase were also highest for Asian/Pacific Islanders (8.92%), followed by Hispanic (7.17%) and Black youth (5.99%).
Among youth aged 15-19 years, the overall incidence of type 2 diabetes exceeded that of type 1 diabetes (19.7 vs. 14.6/100,000).
The incidence of type 2 diabetes may be rising because of increased rates of obesity, as well as increased screening of at-risk youth, the authors say.
And, the editorialists note, obesity is also a risk factor for type 1 diabetes.
Peak incidence of type 1 diabetes occurred at age 10 years, while for type 2 diabetes, the peak was at 16 years. There were also seasonal peaks, occurring in January for type 1 diabetes and in August for type 2 diabetes. Those seasonal patterns have been previously reported; they are possibly because of increased viral infections and decreased sun exposure for the former, and increased physical exams in preparation for school in the latter, the authors speculate.
Dr. Shaw and Dr. Magliano note that the reduced incidence after age 16 years “might simply reflect a failure to diagnose,” suggesting that there will likely be an upturn in incidence in the subsequent decade.
The editorialists also point out: “Not only does the long duration of diabetes that youth-onset leads to cause a large burden of fatal and nonfatal complications, but it magnifies intergenerational effects.”
“When type 2 diabetes is already present before pregnancy, birth outcomes are worse, and the long-term metabolic health of the offspring is adversely affected. This does not bode well for the epidemic of diabetes and its complications.”
The study was funded by the Centers for Disease Control and Prevention and National Institutes of Health. The authors and Dr. Magliano have reported no relevant financial relationships. Dr. Shaw has reported receiving honoraria for lectures and for advisory boards and grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, Sanofi, Roche, Mylan, and Zuellig Pharma.
A version of this article originally appeared on Medscape.com.
The incidence of type 1 and type 2 diabetes continues to rise among children and adolescents in the United States, new data from the SEARCH for Diabetes in Youth study show.
The SEARCH data demonstrate an increase in the youth population aged 0-19 diagnosed with type 1 or type 2 diabetes in five representative U.S. centers. Between 2002 and 2018, the annual incidence rose by about 2% per year for type 1 diabetes and 5% per year for type 2 diabetes. The rates of increase for both types were greater among non-White than White youth.
These increases “will result in an expanding population of young adults at risk of developing early complications of diabetes whose health care needs will exceed those of their peers,” write Lynne E. Wagenknecht, DrPH, of Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues in their article, recently published in The Lancet Diabetes & Endocrinology.
In an accompanying editorial, Jonathan E. Shaw, MD, and Dianna J. Magliano, PhD, both at the Baker Heart and Diabetes Institute, Melbourne, write that one of the most “concerning findings” was a 7%-9% annual increase in the incidence of type 2 diabetes among Hispanic, Asian, and Pacific Islander populations.
“This is a health care crisis in the making. ...Youth and young-adult-onset type 2 diabetes are growing problems leading to poor outcomes and to widening social inequality, adversely affecting a population that might already be disadvantaged. Better information about its natural history, prevention, and management is urgently needed,” they write.
Upward trends in both diabetes types
Overall, 18,169 children and adolescents with type 1 diabetes and 5,293 with type 2 diabetes were identified over the 17-year study period in SEARCH. After adjustment for age, sex, and race/ethnicity, there was a significant increase in type 1 diabetes incidence from 19.5 cases/100,000 population in 2002-2003 to 22.2/100,000 in 2017-2018, a 2.02% annual increase.
The upward trend was even greater for type 2 diabetes, from 9.0/100,000 in 2002-2003 to 17.9/100,000 in 2017-2018, a 5.31% annual increase.
The annual rate of increase in type 1 diabetes was highest among Asian/Pacific Islander youth (4.84%), followed by Hispanic (4.14%) and Black youth (2.93%): All significantly rose over the 17 years.
For type 2 diabetes, significant annual rates of increase were also highest for Asian/Pacific Islanders (8.92%), followed by Hispanic (7.17%) and Black youth (5.99%).
Among youth aged 15-19 years, the overall incidence of type 2 diabetes exceeded that of type 1 diabetes (19.7 vs. 14.6/100,000).
The incidence of type 2 diabetes may be rising because of increased rates of obesity, as well as increased screening of at-risk youth, the authors say.
And, the editorialists note, obesity is also a risk factor for type 1 diabetes.
Peak incidence of type 1 diabetes occurred at age 10 years, while for type 2 diabetes, the peak was at 16 years. There were also seasonal peaks, occurring in January for type 1 diabetes and in August for type 2 diabetes. Those seasonal patterns have been previously reported; they are possibly because of increased viral infections and decreased sun exposure for the former, and increased physical exams in preparation for school in the latter, the authors speculate.
Dr. Shaw and Dr. Magliano note that the reduced incidence after age 16 years “might simply reflect a failure to diagnose,” suggesting that there will likely be an upturn in incidence in the subsequent decade.
The editorialists also point out: “Not only does the long duration of diabetes that youth-onset leads to cause a large burden of fatal and nonfatal complications, but it magnifies intergenerational effects.”
“When type 2 diabetes is already present before pregnancy, birth outcomes are worse, and the long-term metabolic health of the offspring is adversely affected. This does not bode well for the epidemic of diabetes and its complications.”
The study was funded by the Centers for Disease Control and Prevention and National Institutes of Health. The authors and Dr. Magliano have reported no relevant financial relationships. Dr. Shaw has reported receiving honoraria for lectures and for advisory boards and grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, Sanofi, Roche, Mylan, and Zuellig Pharma.
A version of this article originally appeared on Medscape.com.
FROM THE LANCET DIABETES & ENDOCRINOLOGY
APA releases updated eating disorder guidelines
The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.
“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”
Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.
The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.
The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.
The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.
Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.
“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.
A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.
The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.
The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.
A version of this article first appeared on Medscape.com.
The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.
“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”
Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.
The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.
The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.
The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.
Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.
“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.
A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.
The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.
The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.
A version of this article first appeared on Medscape.com.
The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.
“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”
Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.
The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.
The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.
The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.
Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.
“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.
A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.
The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.
The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PSYCHIATRY