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Extended propranolol use boosts success in high-risk infantile hemangioma
Extending oral propranolol treatment up to 12 months of age increased the success rate for high-risk infantile hemangioma, according to results published in Pediatrics.
Previous studies of oral propranol for infantile hemangiomas (IH) have revealed its efficacy, although there is no consensus on the optimal treatment duration. Nonetheless, treatment up to 12 months of age has been proposed if patients don’t respond after 6 months. Infants with high-risk hemangiomas, however, have been excluded from previous studies, authors of the current study explained.
In an open-label study of patients aged 35-150 days the success rate of oral propranolol was 47% after 6 months of treatment. The rate increased to 76% after the initial treatment period, reported Eulalia Baselga, MD, of the department of dermatology at Hospital de la Santa Creu i Sant Pau in Barcelona, and coauthors.
Investigators studied 45 patients from 10 hospitals in Spain and Poland between June 2015 and February 2017. The patients had high-risk IH in the proliferative phase. High-risk hemangiomas were defined as those that were life threatening, at risk for functional impact, disfiguring, or ulcerated nonresponsive to standard wound care measures.
Oral propranolol was administered twice daily at a dosage of 3 mg/kg per day. During the initial treatment period (ITP), patients received propranolol for a minimum of 6 months, and if treatment was not successful, it continued until success or up to 12 months of age.
Patients who achieved success in the initial phase were managed for 3 months with no treatment, and if there was rebound growth, treatment was restarted for up to 6 months at the provider’s discretion.
Treatment was considered a success if the target hemangioma resolved and there was no functional impact. The IH was considered resolved if it disappeared, even if there were minimal telangiectasias, erythema, skin thickening, soft tissue swelling, or the presence of sequelae.
Treatment success was achieved by 21 (47%) patients after 6 months and by 34 (76%) patients by the end of the ITP. Functional impact was determined using the Hemangioma Severity and Hemangioma Dynamic Complication scales. Adverse events, reported by 80% of patients, were resolved by the end of the study and included respiratory syncytial virus bronchiolitis, ulcerated hemangioma, pneumonia and respiratory failure, inguinal hernia, upper respiratory tract infection, dehydration, bronchitis, choking, and thermal burn. Although no patients experienced adverse events that resulted in discontinuation of treatment, 35 events led to temporary discontinuation, primarily due to respiratory events, the authors reported.
The results indicate that “oral propranolol is effective in treating high-risk IH with a favorable safety profile,” the authors concluded.
The study was funded by the Institut de Recherche Pierre Fabre Several authors were employed by or had other relationships with Pierre Fabre. The other authors had no conflicts of interest.
SOURCE: Baselga E et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3866.
Extending oral propranolol treatment up to 12 months of age increased the success rate for high-risk infantile hemangioma, according to results published in Pediatrics.
Previous studies of oral propranol for infantile hemangiomas (IH) have revealed its efficacy, although there is no consensus on the optimal treatment duration. Nonetheless, treatment up to 12 months of age has been proposed if patients don’t respond after 6 months. Infants with high-risk hemangiomas, however, have been excluded from previous studies, authors of the current study explained.
In an open-label study of patients aged 35-150 days the success rate of oral propranolol was 47% after 6 months of treatment. The rate increased to 76% after the initial treatment period, reported Eulalia Baselga, MD, of the department of dermatology at Hospital de la Santa Creu i Sant Pau in Barcelona, and coauthors.
Investigators studied 45 patients from 10 hospitals in Spain and Poland between June 2015 and February 2017. The patients had high-risk IH in the proliferative phase. High-risk hemangiomas were defined as those that were life threatening, at risk for functional impact, disfiguring, or ulcerated nonresponsive to standard wound care measures.
Oral propranolol was administered twice daily at a dosage of 3 mg/kg per day. During the initial treatment period (ITP), patients received propranolol for a minimum of 6 months, and if treatment was not successful, it continued until success or up to 12 months of age.
Patients who achieved success in the initial phase were managed for 3 months with no treatment, and if there was rebound growth, treatment was restarted for up to 6 months at the provider’s discretion.
Treatment was considered a success if the target hemangioma resolved and there was no functional impact. The IH was considered resolved if it disappeared, even if there were minimal telangiectasias, erythema, skin thickening, soft tissue swelling, or the presence of sequelae.
Treatment success was achieved by 21 (47%) patients after 6 months and by 34 (76%) patients by the end of the ITP. Functional impact was determined using the Hemangioma Severity and Hemangioma Dynamic Complication scales. Adverse events, reported by 80% of patients, were resolved by the end of the study and included respiratory syncytial virus bronchiolitis, ulcerated hemangioma, pneumonia and respiratory failure, inguinal hernia, upper respiratory tract infection, dehydration, bronchitis, choking, and thermal burn. Although no patients experienced adverse events that resulted in discontinuation of treatment, 35 events led to temporary discontinuation, primarily due to respiratory events, the authors reported.
The results indicate that “oral propranolol is effective in treating high-risk IH with a favorable safety profile,” the authors concluded.
The study was funded by the Institut de Recherche Pierre Fabre Several authors were employed by or had other relationships with Pierre Fabre. The other authors had no conflicts of interest.
SOURCE: Baselga E et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3866.
Extending oral propranolol treatment up to 12 months of age increased the success rate for high-risk infantile hemangioma, according to results published in Pediatrics.
Previous studies of oral propranol for infantile hemangiomas (IH) have revealed its efficacy, although there is no consensus on the optimal treatment duration. Nonetheless, treatment up to 12 months of age has been proposed if patients don’t respond after 6 months. Infants with high-risk hemangiomas, however, have been excluded from previous studies, authors of the current study explained.
In an open-label study of patients aged 35-150 days the success rate of oral propranolol was 47% after 6 months of treatment. The rate increased to 76% after the initial treatment period, reported Eulalia Baselga, MD, of the department of dermatology at Hospital de la Santa Creu i Sant Pau in Barcelona, and coauthors.
Investigators studied 45 patients from 10 hospitals in Spain and Poland between June 2015 and February 2017. The patients had high-risk IH in the proliferative phase. High-risk hemangiomas were defined as those that were life threatening, at risk for functional impact, disfiguring, or ulcerated nonresponsive to standard wound care measures.
Oral propranolol was administered twice daily at a dosage of 3 mg/kg per day. During the initial treatment period (ITP), patients received propranolol for a minimum of 6 months, and if treatment was not successful, it continued until success or up to 12 months of age.
Patients who achieved success in the initial phase were managed for 3 months with no treatment, and if there was rebound growth, treatment was restarted for up to 6 months at the provider’s discretion.
Treatment was considered a success if the target hemangioma resolved and there was no functional impact. The IH was considered resolved if it disappeared, even if there were minimal telangiectasias, erythema, skin thickening, soft tissue swelling, or the presence of sequelae.
Treatment success was achieved by 21 (47%) patients after 6 months and by 34 (76%) patients by the end of the ITP. Functional impact was determined using the Hemangioma Severity and Hemangioma Dynamic Complication scales. Adverse events, reported by 80% of patients, were resolved by the end of the study and included respiratory syncytial virus bronchiolitis, ulcerated hemangioma, pneumonia and respiratory failure, inguinal hernia, upper respiratory tract infection, dehydration, bronchitis, choking, and thermal burn. Although no patients experienced adverse events that resulted in discontinuation of treatment, 35 events led to temporary discontinuation, primarily due to respiratory events, the authors reported.
The results indicate that “oral propranolol is effective in treating high-risk IH with a favorable safety profile,” the authors concluded.
The study was funded by the Institut de Recherche Pierre Fabre Several authors were employed by or had other relationships with Pierre Fabre. The other authors had no conflicts of interest.
SOURCE: Baselga E et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3866.
FROM PEDIATRICS
Key clinical point:
Major finding: After 6 months of treatment, the success rate was 47%, and it rose to 76% at the end of the treatment period.
Study details: A phase 3 study of 45 patients aged 35-150 days with high-risk IH.
Disclosures: The study was funded by the Institut de Recherche Pierre Fabre Several authors were employed by or had other relationships with Pierre Fabre. The other authors had no conflicts of interest.
Source: Baselga E et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3866
CDC releases guidelines for pediatric mTBI
and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
FROM JAMA PEDIATRICS
First CAR T-cell therapy approved in Canada
Health Canada has authorized use of tisagenlecleucel (Kymriah™), making it the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.
Tisagenlecleucel (formerly CTL019) is approved to treat patients ages 3 to 25 with B-cell acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.
Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.
Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers, and Novartis is enhancing manufacturing capacity to meet patient needs.
Tisagenlecleucel has been studied in a pair of phase 2 trials—ELIANA and JULIET.
JULIET trial
JULIET enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.
The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.
The 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).
These results were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).
ELIANA trial
ELIANA included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).
All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.
The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi. All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
Ninety-five percent of patients had AEs thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 AEs was 73%.
AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).
These results were published in The New England Journal of Medicine in February.
Health Canada has authorized use of tisagenlecleucel (Kymriah™), making it the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.
Tisagenlecleucel (formerly CTL019) is approved to treat patients ages 3 to 25 with B-cell acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.
Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.
Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers, and Novartis is enhancing manufacturing capacity to meet patient needs.
Tisagenlecleucel has been studied in a pair of phase 2 trials—ELIANA and JULIET.
JULIET trial
JULIET enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.
The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.
The 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).
These results were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).
ELIANA trial
ELIANA included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).
All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.
The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi. All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
Ninety-five percent of patients had AEs thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 AEs was 73%.
AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).
These results were published in The New England Journal of Medicine in February.
Health Canada has authorized use of tisagenlecleucel (Kymriah™), making it the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.
Tisagenlecleucel (formerly CTL019) is approved to treat patients ages 3 to 25 with B-cell acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.
Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.
Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers, and Novartis is enhancing manufacturing capacity to meet patient needs.
Tisagenlecleucel has been studied in a pair of phase 2 trials—ELIANA and JULIET.
JULIET trial
JULIET enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.
The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.
The 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).
These results were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).
ELIANA trial
ELIANA included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).
All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.
The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi. All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
Ninety-five percent of patients had AEs thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 AEs was 73%.
AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).
These results were published in The New England Journal of Medicine in February.
Children born from ART at increased risk of developing arterial hypertension
Children born from assisted reproductive technologies such as in vitro fertilization and intracytoplasmic sperm injection may be at risk of developing arterial hypertension due to premature vascular aging, according to a study published in the Journal of the American College of Cardiology.
In a previous study, Emrush Rexhaj, MD, director of arterial hypertension and altitude medicine at Inselspital, University Hospital, Bern, Switzerland, and his colleagues assessed vascular function in participants who were born with assisted reproductive technology (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI); the investigators found vascular dysfunction in this patient population not “related to parental factors but to the ART procedure itself,” they said.
Dr. Rexhaj and his colleagues then reassessed vascular function in 54 participants (mean age 16.5 years old) who returned from the previous study 5 years after the initial assessment and compared the results with 43 matched patients in a control group (mean age, 17.4 years). There were no significant differences regarding body mass index, lipid, creatinine, electrolyte plasma concentrations, high-sensitive C-reactive protein, birth weight, and gestational age between children in either group, as well as no significant differences in maternal BMI, cardiovascular risk profile, and smoking status.
The investigators – with Théo A. Meister, MD, also of the university, as a joint lead author with Dr. Rexhaj – performed blinded endothelium-dependent and endothelium-independent vasodilation of the brachial artery in a supine position at room temperature and after 15 minutes of rest. They also measured carotid intima-media thickness (IMT), large artery stiffness, 24-hour ambulatory blood pressure monitoring, and short-term blood pressure variability.
“It only took five years for differences in arterial blood pressure to show,” Dr. Rexhaj stated in a press release. “This is a rapidly growing population and apparently healthy children are showing serious signs of concern for early cardiovascular risk, especially when it comes to arterial hypertension.”
Specifically, there was an approximately 25% reduction in flow-mediated dilation in the ART group (7%) compared with the control group (9%), which the investigators attributed to endothelial dysfunction (P less than .001). In ART patients, carotid IMT (463 mm) and carotid pulse-wave velocity (7.7 m/s) was significantly increased, compared with carotid IMT (435 mm; P less than .01) and pulse-wave velocity (7.2 m/s; P equals .033) in the control group.
With regard to arterial hypertension, 24-hour systolic blood pressure in the ART group (120 mm Hg) was “markedly” higher than in the control group (116 mm Hg; P equals .02); 24-hour diastolic blood pressure was also significantly higher in the ART group (71 mm Hg) compared with the control group (69 mm Hg; P equals .03). Investigators noted 8 of the 52 patients (15%) in the ART group met clinical criteria for arterial hypertension according to ambulatory blood pressure monitoring, compared with 1 of the 40 patients (2%) in the control group.
“The increased prevalence of arterial hypertension in ART participants is what is most concerning,” Dr. Rexhaj stated in the release. “There is growing evidence that ART alters the blood vessels in children, but the long-term consequences were not known. We now know that this places ART children at a six times higher rate of hypertension than children conceived naturally.”
The investigators cited as a limitation the fact that they studied only children born from singleton births recruited from a single center, which may have a lower cardiovascular risk profile than other patient populations.
This study was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology and Mach-Gaensslen Stiftung (Schweiz). The authors reported no conflicts of interest.
SOURCE: Meister TA et al. J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.06.060.
Clinicians should be vigilant in detecting early cardiovascular problems in children born from ART, Larry A. Weinrauch, MD, of Harvard Medical School, Boston, and his colleagues wrote in a joint editorial comment. While the sixfold higher risk of arterial hypertension was obtained from an ambulatory blood pressure monitoring that was not repeated, the relative risk of cardiovascular problems for singleton births could be a sign that a greater risk for vascular aging exists with multiple births.
“This observation, derived from a relatively small cohort, may actually understate the importance of this problem for ART populations because higher risk populations for development of hypertension (e.g., multiple birth pregnancies) and those resulting from maternal factors of excess risk (e.g., eclampsia, chronic hypertension, diabetes, obesity) were excluded from the study,” Dr. Weinrauch and his colleagues said.
The authors cited the pediatric hypertension clinical practice guidelines of annual in-office hypertension screening after 3 years of age and noted that certain high-risk groups, such as patients with repaired aortic coarctation and chronic kidney disease, should be screened “at every health encounter.
“If adolescent hypertension risk is really sixfold higher in ART patients (and potentially subsequent generations), consequences for longevity will be vast given the millions of patients whose births were achieved by using ART methods,” wrote Dr. Weinrauch and his colleagues. “Early study, detection, and treatment of ART-conceived individuals may be the appropriate ounce of prevention.”
Dr. Weinrauch is with Harvard Medical School, Marie D. Gerhard-Herman, MD, is with Brigham and Women’s Hospital, and Michael M. Mendelson, MD, is with Boston Children’s Hospital, all in Boston. These comments summarize their editorial in response to Meister et al. (J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.07.013). Dr. Gerhard-Herman is supported by the Progeria Research Foundation and Dr. Mendelson is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. They reported no other relevant conflicts of interest.
Clinicians should be vigilant in detecting early cardiovascular problems in children born from ART, Larry A. Weinrauch, MD, of Harvard Medical School, Boston, and his colleagues wrote in a joint editorial comment. While the sixfold higher risk of arterial hypertension was obtained from an ambulatory blood pressure monitoring that was not repeated, the relative risk of cardiovascular problems for singleton births could be a sign that a greater risk for vascular aging exists with multiple births.
“This observation, derived from a relatively small cohort, may actually understate the importance of this problem for ART populations because higher risk populations for development of hypertension (e.g., multiple birth pregnancies) and those resulting from maternal factors of excess risk (e.g., eclampsia, chronic hypertension, diabetes, obesity) were excluded from the study,” Dr. Weinrauch and his colleagues said.
The authors cited the pediatric hypertension clinical practice guidelines of annual in-office hypertension screening after 3 years of age and noted that certain high-risk groups, such as patients with repaired aortic coarctation and chronic kidney disease, should be screened “at every health encounter.
“If adolescent hypertension risk is really sixfold higher in ART patients (and potentially subsequent generations), consequences for longevity will be vast given the millions of patients whose births were achieved by using ART methods,” wrote Dr. Weinrauch and his colleagues. “Early study, detection, and treatment of ART-conceived individuals may be the appropriate ounce of prevention.”
Dr. Weinrauch is with Harvard Medical School, Marie D. Gerhard-Herman, MD, is with Brigham and Women’s Hospital, and Michael M. Mendelson, MD, is with Boston Children’s Hospital, all in Boston. These comments summarize their editorial in response to Meister et al. (J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.07.013). Dr. Gerhard-Herman is supported by the Progeria Research Foundation and Dr. Mendelson is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. They reported no other relevant conflicts of interest.
Clinicians should be vigilant in detecting early cardiovascular problems in children born from ART, Larry A. Weinrauch, MD, of Harvard Medical School, Boston, and his colleagues wrote in a joint editorial comment. While the sixfold higher risk of arterial hypertension was obtained from an ambulatory blood pressure monitoring that was not repeated, the relative risk of cardiovascular problems for singleton births could be a sign that a greater risk for vascular aging exists with multiple births.
“This observation, derived from a relatively small cohort, may actually understate the importance of this problem for ART populations because higher risk populations for development of hypertension (e.g., multiple birth pregnancies) and those resulting from maternal factors of excess risk (e.g., eclampsia, chronic hypertension, diabetes, obesity) were excluded from the study,” Dr. Weinrauch and his colleagues said.
The authors cited the pediatric hypertension clinical practice guidelines of annual in-office hypertension screening after 3 years of age and noted that certain high-risk groups, such as patients with repaired aortic coarctation and chronic kidney disease, should be screened “at every health encounter.
“If adolescent hypertension risk is really sixfold higher in ART patients (and potentially subsequent generations), consequences for longevity will be vast given the millions of patients whose births were achieved by using ART methods,” wrote Dr. Weinrauch and his colleagues. “Early study, detection, and treatment of ART-conceived individuals may be the appropriate ounce of prevention.”
Dr. Weinrauch is with Harvard Medical School, Marie D. Gerhard-Herman, MD, is with Brigham and Women’s Hospital, and Michael M. Mendelson, MD, is with Boston Children’s Hospital, all in Boston. These comments summarize their editorial in response to Meister et al. (J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.07.013). Dr. Gerhard-Herman is supported by the Progeria Research Foundation and Dr. Mendelson is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. They reported no other relevant conflicts of interest.
Children born from assisted reproductive technologies such as in vitro fertilization and intracytoplasmic sperm injection may be at risk of developing arterial hypertension due to premature vascular aging, according to a study published in the Journal of the American College of Cardiology.
In a previous study, Emrush Rexhaj, MD, director of arterial hypertension and altitude medicine at Inselspital, University Hospital, Bern, Switzerland, and his colleagues assessed vascular function in participants who were born with assisted reproductive technology (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI); the investigators found vascular dysfunction in this patient population not “related to parental factors but to the ART procedure itself,” they said.
Dr. Rexhaj and his colleagues then reassessed vascular function in 54 participants (mean age 16.5 years old) who returned from the previous study 5 years after the initial assessment and compared the results with 43 matched patients in a control group (mean age, 17.4 years). There were no significant differences regarding body mass index, lipid, creatinine, electrolyte plasma concentrations, high-sensitive C-reactive protein, birth weight, and gestational age between children in either group, as well as no significant differences in maternal BMI, cardiovascular risk profile, and smoking status.
The investigators – with Théo A. Meister, MD, also of the university, as a joint lead author with Dr. Rexhaj – performed blinded endothelium-dependent and endothelium-independent vasodilation of the brachial artery in a supine position at room temperature and after 15 minutes of rest. They also measured carotid intima-media thickness (IMT), large artery stiffness, 24-hour ambulatory blood pressure monitoring, and short-term blood pressure variability.
“It only took five years for differences in arterial blood pressure to show,” Dr. Rexhaj stated in a press release. “This is a rapidly growing population and apparently healthy children are showing serious signs of concern for early cardiovascular risk, especially when it comes to arterial hypertension.”
Specifically, there was an approximately 25% reduction in flow-mediated dilation in the ART group (7%) compared with the control group (9%), which the investigators attributed to endothelial dysfunction (P less than .001). In ART patients, carotid IMT (463 mm) and carotid pulse-wave velocity (7.7 m/s) was significantly increased, compared with carotid IMT (435 mm; P less than .01) and pulse-wave velocity (7.2 m/s; P equals .033) in the control group.
With regard to arterial hypertension, 24-hour systolic blood pressure in the ART group (120 mm Hg) was “markedly” higher than in the control group (116 mm Hg; P equals .02); 24-hour diastolic blood pressure was also significantly higher in the ART group (71 mm Hg) compared with the control group (69 mm Hg; P equals .03). Investigators noted 8 of the 52 patients (15%) in the ART group met clinical criteria for arterial hypertension according to ambulatory blood pressure monitoring, compared with 1 of the 40 patients (2%) in the control group.
“The increased prevalence of arterial hypertension in ART participants is what is most concerning,” Dr. Rexhaj stated in the release. “There is growing evidence that ART alters the blood vessels in children, but the long-term consequences were not known. We now know that this places ART children at a six times higher rate of hypertension than children conceived naturally.”
The investigators cited as a limitation the fact that they studied only children born from singleton births recruited from a single center, which may have a lower cardiovascular risk profile than other patient populations.
This study was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology and Mach-Gaensslen Stiftung (Schweiz). The authors reported no conflicts of interest.
SOURCE: Meister TA et al. J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.06.060.
Children born from assisted reproductive technologies such as in vitro fertilization and intracytoplasmic sperm injection may be at risk of developing arterial hypertension due to premature vascular aging, according to a study published in the Journal of the American College of Cardiology.
In a previous study, Emrush Rexhaj, MD, director of arterial hypertension and altitude medicine at Inselspital, University Hospital, Bern, Switzerland, and his colleagues assessed vascular function in participants who were born with assisted reproductive technology (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI); the investigators found vascular dysfunction in this patient population not “related to parental factors but to the ART procedure itself,” they said.
Dr. Rexhaj and his colleagues then reassessed vascular function in 54 participants (mean age 16.5 years old) who returned from the previous study 5 years after the initial assessment and compared the results with 43 matched patients in a control group (mean age, 17.4 years). There were no significant differences regarding body mass index, lipid, creatinine, electrolyte plasma concentrations, high-sensitive C-reactive protein, birth weight, and gestational age between children in either group, as well as no significant differences in maternal BMI, cardiovascular risk profile, and smoking status.
The investigators – with Théo A. Meister, MD, also of the university, as a joint lead author with Dr. Rexhaj – performed blinded endothelium-dependent and endothelium-independent vasodilation of the brachial artery in a supine position at room temperature and after 15 minutes of rest. They also measured carotid intima-media thickness (IMT), large artery stiffness, 24-hour ambulatory blood pressure monitoring, and short-term blood pressure variability.
“It only took five years for differences in arterial blood pressure to show,” Dr. Rexhaj stated in a press release. “This is a rapidly growing population and apparently healthy children are showing serious signs of concern for early cardiovascular risk, especially when it comes to arterial hypertension.”
Specifically, there was an approximately 25% reduction in flow-mediated dilation in the ART group (7%) compared with the control group (9%), which the investigators attributed to endothelial dysfunction (P less than .001). In ART patients, carotid IMT (463 mm) and carotid pulse-wave velocity (7.7 m/s) was significantly increased, compared with carotid IMT (435 mm; P less than .01) and pulse-wave velocity (7.2 m/s; P equals .033) in the control group.
With regard to arterial hypertension, 24-hour systolic blood pressure in the ART group (120 mm Hg) was “markedly” higher than in the control group (116 mm Hg; P equals .02); 24-hour diastolic blood pressure was also significantly higher in the ART group (71 mm Hg) compared with the control group (69 mm Hg; P equals .03). Investigators noted 8 of the 52 patients (15%) in the ART group met clinical criteria for arterial hypertension according to ambulatory blood pressure monitoring, compared with 1 of the 40 patients (2%) in the control group.
“The increased prevalence of arterial hypertension in ART participants is what is most concerning,” Dr. Rexhaj stated in the release. “There is growing evidence that ART alters the blood vessels in children, but the long-term consequences were not known. We now know that this places ART children at a six times higher rate of hypertension than children conceived naturally.”
The investigators cited as a limitation the fact that they studied only children born from singleton births recruited from a single center, which may have a lower cardiovascular risk profile than other patient populations.
This study was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology and Mach-Gaensslen Stiftung (Schweiz). The authors reported no conflicts of interest.
SOURCE: Meister TA et al. J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.06.060.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point:
Major finding: In the ART group, 24-hour systolic blood pressure was significantly higher than in the control group (120 mm Hg vs. 116 mm Hg), and 24-hour diastolic blood pressure was also significantly higher in the ART group compared with the control group (71 mm Hg vs. 69 mm Hg).
Study details: A reassessment of 54 children born from ART.
Disclosures: This study was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology and Mach-Gaensslen Stiftung (Schweiz). The authors reported no conflicts of interest.
Source: Meister TA et al. J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.06.060.
Childhood-onset SLE has major impact in adult life
The majority of adults with childhood-onset systemic lupus erythematosus in a longitudinal Dutch study developed significant damage at a young age, remain on corticosteroids in adulthood, and have an impaired health-related quality of life.
The findings in the study, dubbed Childhood-Onset SLE in the Netherlands (CHILL-NL), highlighted the need for preventive screening measures to be put in place before the age of 30 to facilitate a better outcome for patients, who still face high morbidity from childhood-onset systemic lupus erythematosus (cSLE) despite improved survival. Such information is helpful to “answer questions from children and parents regarding the future course of the disease,” wrote Noortje Groot, PhD, of the department of pediatric rheumatology at Erasmus Medical Center–Sophia Children’s Hospital in Rotterdam, the Netherlands, and her colleagues. The report is in Arthritis & Rheumatology.
The current study included all adult SLE patients treated in any Dutch public hospital during the period of November 2013 to April 2016 who were diagnosed with the autoimmune disease prior to their 18th birthday.
All 111 patients involved in the study were seen for a 1.5-hour visit at Erasmus University Medical Center or a local hospital of their choice. During the appointment, a medical history was taken, a physical examination was performed, and the patients completed questionnaires on health-related quality of life (HRQOL).
The average age of patients at the study visit was 33 years, 91% were female, and 72% were white. Median disease duration was 20 years and disease activity was low (median SLE Disease Activity Index 2000 [SLEDAI-2k] = 4). Low complement (32%), skin rashes (14%), and proteinuria (13%) were the most common SLEDAI items reported.
Overall, 68% of the cohort (n = 76) were taking hydroxychloroquine (HCQ), 29% of whom (n = 22) were taking it as monotherapy.
Furthermore, 68% of patients at the study visit were taking corticosteroids and/or non-HCQ disease-modifying antirheumatic drugs (DMARDs), and just over half (51%) of patients (n = 56) were taking corticosteroids either alone or with a non-HCQ DMARD.
“This [finding] is worrying as corticosteroids are associated with the development of damage. Patients are certainly eager to limit corticosteroid use, as almost all patients in the CHILL-NL cohort reported to have negative experiences with prednisone regarding their physical appearance and or mental well-being,” the study authors wrote.
Results also showed that 62% of the patients had damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems.
Most organ systems became involved within the first 2 years of diagnosis, but after 5 years of disease the nature of disease manifestations tended to shift to damage such as myocardial infarctions.
Notably, after 10-20 years, when cSLE patients were in their early 20s and 30s, significant damage had occurred in more than half of the patients, the authors noted.
“This shift to damage has also been observed in adult-onset SLE patients and urges for preventative screening measures of such (cardiovascular) damage and healthy lifestyle advice (healthy diet, regular exercise, abstinence from smoking),” they wrote.
Multivariate logistic regression showed that damage accrual was associated with disease duration (odds ratio, 1.15; P less than .001), antiphospholipid‐antibody positivity (OR, 3.56; P = .026), and hypertension (OR, 3.21; P = .043). On the other hand, current HCQ monotherapy was associated with an SLICC-Damage Index score of 0 (OR, 0.16; P = .009).
The HRQOL of the cohort, assessed via the Short Form–36, was also impaired compared with the general population, the researchers discovered. For example, the presence of damage reduced HRQOL in one domain, and high disease activity, defined as SLEDAI-2k of 8 or more, strongly reduced HRQOL in four of eight domains. Changes in physical appearance lowered HRQOL in seven of eight domains.
“HRQOL of adults with cSLE is impaired and affected by other factors than disease activity or damage alone. By identifying and addressing these factors, like physical appearance and potentially coping styles, HRQOL may be improved,” they advised.
The study was supported financially by the Dutch Arthritis Foundation and the Dutch national patient association for lupus, antiphospholipid syndrome, scleroderma, and mixed connective tissue diseases.
SOURCE: Groot N et al. Arthritis Rheumatol. 2018 Aug 27. doi: 10.1002/art.40697
The majority of adults with childhood-onset systemic lupus erythematosus in a longitudinal Dutch study developed significant damage at a young age, remain on corticosteroids in adulthood, and have an impaired health-related quality of life.
The findings in the study, dubbed Childhood-Onset SLE in the Netherlands (CHILL-NL), highlighted the need for preventive screening measures to be put in place before the age of 30 to facilitate a better outcome for patients, who still face high morbidity from childhood-onset systemic lupus erythematosus (cSLE) despite improved survival. Such information is helpful to “answer questions from children and parents regarding the future course of the disease,” wrote Noortje Groot, PhD, of the department of pediatric rheumatology at Erasmus Medical Center–Sophia Children’s Hospital in Rotterdam, the Netherlands, and her colleagues. The report is in Arthritis & Rheumatology.
The current study included all adult SLE patients treated in any Dutch public hospital during the period of November 2013 to April 2016 who were diagnosed with the autoimmune disease prior to their 18th birthday.
All 111 patients involved in the study were seen for a 1.5-hour visit at Erasmus University Medical Center or a local hospital of their choice. During the appointment, a medical history was taken, a physical examination was performed, and the patients completed questionnaires on health-related quality of life (HRQOL).
The average age of patients at the study visit was 33 years, 91% were female, and 72% were white. Median disease duration was 20 years and disease activity was low (median SLE Disease Activity Index 2000 [SLEDAI-2k] = 4). Low complement (32%), skin rashes (14%), and proteinuria (13%) were the most common SLEDAI items reported.
Overall, 68% of the cohort (n = 76) were taking hydroxychloroquine (HCQ), 29% of whom (n = 22) were taking it as monotherapy.
Furthermore, 68% of patients at the study visit were taking corticosteroids and/or non-HCQ disease-modifying antirheumatic drugs (DMARDs), and just over half (51%) of patients (n = 56) were taking corticosteroids either alone or with a non-HCQ DMARD.
“This [finding] is worrying as corticosteroids are associated with the development of damage. Patients are certainly eager to limit corticosteroid use, as almost all patients in the CHILL-NL cohort reported to have negative experiences with prednisone regarding their physical appearance and or mental well-being,” the study authors wrote.
Results also showed that 62% of the patients had damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems.
Most organ systems became involved within the first 2 years of diagnosis, but after 5 years of disease the nature of disease manifestations tended to shift to damage such as myocardial infarctions.
Notably, after 10-20 years, when cSLE patients were in their early 20s and 30s, significant damage had occurred in more than half of the patients, the authors noted.
“This shift to damage has also been observed in adult-onset SLE patients and urges for preventative screening measures of such (cardiovascular) damage and healthy lifestyle advice (healthy diet, regular exercise, abstinence from smoking),” they wrote.
Multivariate logistic regression showed that damage accrual was associated with disease duration (odds ratio, 1.15; P less than .001), antiphospholipid‐antibody positivity (OR, 3.56; P = .026), and hypertension (OR, 3.21; P = .043). On the other hand, current HCQ monotherapy was associated with an SLICC-Damage Index score of 0 (OR, 0.16; P = .009).
The HRQOL of the cohort, assessed via the Short Form–36, was also impaired compared with the general population, the researchers discovered. For example, the presence of damage reduced HRQOL in one domain, and high disease activity, defined as SLEDAI-2k of 8 or more, strongly reduced HRQOL in four of eight domains. Changes in physical appearance lowered HRQOL in seven of eight domains.
“HRQOL of adults with cSLE is impaired and affected by other factors than disease activity or damage alone. By identifying and addressing these factors, like physical appearance and potentially coping styles, HRQOL may be improved,” they advised.
The study was supported financially by the Dutch Arthritis Foundation and the Dutch national patient association for lupus, antiphospholipid syndrome, scleroderma, and mixed connective tissue diseases.
SOURCE: Groot N et al. Arthritis Rheumatol. 2018 Aug 27. doi: 10.1002/art.40697
The majority of adults with childhood-onset systemic lupus erythematosus in a longitudinal Dutch study developed significant damage at a young age, remain on corticosteroids in adulthood, and have an impaired health-related quality of life.
The findings in the study, dubbed Childhood-Onset SLE in the Netherlands (CHILL-NL), highlighted the need for preventive screening measures to be put in place before the age of 30 to facilitate a better outcome for patients, who still face high morbidity from childhood-onset systemic lupus erythematosus (cSLE) despite improved survival. Such information is helpful to “answer questions from children and parents regarding the future course of the disease,” wrote Noortje Groot, PhD, of the department of pediatric rheumatology at Erasmus Medical Center–Sophia Children’s Hospital in Rotterdam, the Netherlands, and her colleagues. The report is in Arthritis & Rheumatology.
The current study included all adult SLE patients treated in any Dutch public hospital during the period of November 2013 to April 2016 who were diagnosed with the autoimmune disease prior to their 18th birthday.
All 111 patients involved in the study were seen for a 1.5-hour visit at Erasmus University Medical Center or a local hospital of their choice. During the appointment, a medical history was taken, a physical examination was performed, and the patients completed questionnaires on health-related quality of life (HRQOL).
The average age of patients at the study visit was 33 years, 91% were female, and 72% were white. Median disease duration was 20 years and disease activity was low (median SLE Disease Activity Index 2000 [SLEDAI-2k] = 4). Low complement (32%), skin rashes (14%), and proteinuria (13%) were the most common SLEDAI items reported.
Overall, 68% of the cohort (n = 76) were taking hydroxychloroquine (HCQ), 29% of whom (n = 22) were taking it as monotherapy.
Furthermore, 68% of patients at the study visit were taking corticosteroids and/or non-HCQ disease-modifying antirheumatic drugs (DMARDs), and just over half (51%) of patients (n = 56) were taking corticosteroids either alone or with a non-HCQ DMARD.
“This [finding] is worrying as corticosteroids are associated with the development of damage. Patients are certainly eager to limit corticosteroid use, as almost all patients in the CHILL-NL cohort reported to have negative experiences with prednisone regarding their physical appearance and or mental well-being,” the study authors wrote.
Results also showed that 62% of the patients had damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems.
Most organ systems became involved within the first 2 years of diagnosis, but after 5 years of disease the nature of disease manifestations tended to shift to damage such as myocardial infarctions.
Notably, after 10-20 years, when cSLE patients were in their early 20s and 30s, significant damage had occurred in more than half of the patients, the authors noted.
“This shift to damage has also been observed in adult-onset SLE patients and urges for preventative screening measures of such (cardiovascular) damage and healthy lifestyle advice (healthy diet, regular exercise, abstinence from smoking),” they wrote.
Multivariate logistic regression showed that damage accrual was associated with disease duration (odds ratio, 1.15; P less than .001), antiphospholipid‐antibody positivity (OR, 3.56; P = .026), and hypertension (OR, 3.21; P = .043). On the other hand, current HCQ monotherapy was associated with an SLICC-Damage Index score of 0 (OR, 0.16; P = .009).
The HRQOL of the cohort, assessed via the Short Form–36, was also impaired compared with the general population, the researchers discovered. For example, the presence of damage reduced HRQOL in one domain, and high disease activity, defined as SLEDAI-2k of 8 or more, strongly reduced HRQOL in four of eight domains. Changes in physical appearance lowered HRQOL in seven of eight domains.
“HRQOL of adults with cSLE is impaired and affected by other factors than disease activity or damage alone. By identifying and addressing these factors, like physical appearance and potentially coping styles, HRQOL may be improved,” they advised.
The study was supported financially by the Dutch Arthritis Foundation and the Dutch national patient association for lupus, antiphospholipid syndrome, scleroderma, and mixed connective tissue diseases.
SOURCE: Groot N et al. Arthritis Rheumatol. 2018 Aug 27. doi: 10.1002/art.40697
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: Among 111 patients, 62% had damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems.
Study details: Adult SLE patients diagnosed prior to their 18th birthday who were treated during November 2013 to April 2016 in any Dutch public hospital.
Disclosures: The study was supported financially by the Dutch Arthritis Foundation and the Dutch national patient association for lupus, antiphospholipid syndrome, scleroderma, and mixed connective tissue diseases.
Source: Groot N et al. Arthritis Rheumatol. 2018 Aug 27. doi: 10.1002/art.40697.
Escalating MTX appears superior for T-ALL
Escalating methotrexate (MTX) may produce better outcomes than high-dose MTX in children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), according to research published in the Journal of Clinical Oncology.
Researchers compared escalating and high-dose MTX given with the augmented Berlin-Frankfurt-Munster regimen in patients with T-ALL.
Disease-free survival (DFS) and overall survival (OS) rates were significantly higher among patients who received escalating MTX.
The improved survival outcomes in this trial, AALL0434, are the “opposite effect” of what was observed in a parallel trial, AALL0232. In that trial, high-dose MTX was superior to the escalating strategy in patients with B-cell acute lymphoblastic leukemia (B-ALL).
The parallel trial design was used because of the known differences between T-ALL and B-ALL in sensitivity to MTX and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Minneapolis Hospital, and his coauthors.
The AALL0434 study included 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia. They were randomized to post-induction therapy that included either escalating intravenous MTX or high-dose MTX.
The escalating regimen was superior to high-dose MTX, according to investigators.
The 5-year DFS rate was 91.5% with escalating MTX and 85.3% with high-dose MTX (P=0.005). The 5-year OS rate was 93.7% and 89.4%, respectively (P=0.036).
In contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose MTX produced superior 5-year event-free survival and OS. This led Dr. Winter and his colleagues to speculate on how the findings could be reconciled.
Neither trial was a strict comparison of two different MTX schedules, due to differences in doses of pegaspargase, mercaptopurine, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.
Of note, patients randomized to escalated MTX had two additional doses of pegaspargase. Enhanced asparagine depletion in that arm may have prevented relapse events, the investigators said.
They also said differences in adherence could have played a role, as the cost and time burden of the escalating MTX approach are “substantially less” than the high-dose approach.
The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved DFS.
AALL0434 was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. His coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.
Escalating methotrexate (MTX) may produce better outcomes than high-dose MTX in children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), according to research published in the Journal of Clinical Oncology.
Researchers compared escalating and high-dose MTX given with the augmented Berlin-Frankfurt-Munster regimen in patients with T-ALL.
Disease-free survival (DFS) and overall survival (OS) rates were significantly higher among patients who received escalating MTX.
The improved survival outcomes in this trial, AALL0434, are the “opposite effect” of what was observed in a parallel trial, AALL0232. In that trial, high-dose MTX was superior to the escalating strategy in patients with B-cell acute lymphoblastic leukemia (B-ALL).
The parallel trial design was used because of the known differences between T-ALL and B-ALL in sensitivity to MTX and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Minneapolis Hospital, and his coauthors.
The AALL0434 study included 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia. They were randomized to post-induction therapy that included either escalating intravenous MTX or high-dose MTX.
The escalating regimen was superior to high-dose MTX, according to investigators.
The 5-year DFS rate was 91.5% with escalating MTX and 85.3% with high-dose MTX (P=0.005). The 5-year OS rate was 93.7% and 89.4%, respectively (P=0.036).
In contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose MTX produced superior 5-year event-free survival and OS. This led Dr. Winter and his colleagues to speculate on how the findings could be reconciled.
Neither trial was a strict comparison of two different MTX schedules, due to differences in doses of pegaspargase, mercaptopurine, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.
Of note, patients randomized to escalated MTX had two additional doses of pegaspargase. Enhanced asparagine depletion in that arm may have prevented relapse events, the investigators said.
They also said differences in adherence could have played a role, as the cost and time burden of the escalating MTX approach are “substantially less” than the high-dose approach.
The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved DFS.
AALL0434 was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. His coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.
Escalating methotrexate (MTX) may produce better outcomes than high-dose MTX in children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), according to research published in the Journal of Clinical Oncology.
Researchers compared escalating and high-dose MTX given with the augmented Berlin-Frankfurt-Munster regimen in patients with T-ALL.
Disease-free survival (DFS) and overall survival (OS) rates were significantly higher among patients who received escalating MTX.
The improved survival outcomes in this trial, AALL0434, are the “opposite effect” of what was observed in a parallel trial, AALL0232. In that trial, high-dose MTX was superior to the escalating strategy in patients with B-cell acute lymphoblastic leukemia (B-ALL).
The parallel trial design was used because of the known differences between T-ALL and B-ALL in sensitivity to MTX and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Minneapolis Hospital, and his coauthors.
The AALL0434 study included 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia. They were randomized to post-induction therapy that included either escalating intravenous MTX or high-dose MTX.
The escalating regimen was superior to high-dose MTX, according to investigators.
The 5-year DFS rate was 91.5% with escalating MTX and 85.3% with high-dose MTX (P=0.005). The 5-year OS rate was 93.7% and 89.4%, respectively (P=0.036).
In contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose MTX produced superior 5-year event-free survival and OS. This led Dr. Winter and his colleagues to speculate on how the findings could be reconciled.
Neither trial was a strict comparison of two different MTX schedules, due to differences in doses of pegaspargase, mercaptopurine, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.
Of note, patients randomized to escalated MTX had two additional doses of pegaspargase. Enhanced asparagine depletion in that arm may have prevented relapse events, the investigators said.
They also said differences in adherence could have played a role, as the cost and time burden of the escalating MTX approach are “substantially less” than the high-dose approach.
The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved DFS.
AALL0434 was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. His coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.
CAR T-cell therapy will soon be available in England, NHS says
The National Health Service (NHS) of England has announced that tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy, will soon be available for certain leukemia patients.
Tisagenlecleucel will be made available through the Cancer Drugs Fund, and patients could potentially begin receiving the treatment within weeks.
NHS England struck a deal with Novartis to lower the price of tisagenlecleucel, which costs around £282,000 per patient at its full list price. The discount offered to the NHS is confidential.
Tisagenlecleucel was recently approved by the European Commission (EC) to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.
The EC also approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
However, tisagenlecleucel will only be available for ALL patients in England, at least initially. A decision has not been made regarding funding for tisagenlecleucel in DLBCL, and Novartis previously decided to launch tisagenlecleucel in ALL first.
“It’s fantastic news for children and young people with this form of leukemia that CAR T-cell therapy will be made available on the NHS, making them the first in Europe to have routine access to this exciting new type of immunotherapy,” said Charles Swanton, Cancer Research UK’s chief clinician.
The first three NHS hospitals to go through the international accreditation process for the provision of tisagenlecleucel are in London, Manchester, and Newcastle. Subject to passing accreditation requirements, the first treatments could begin in a matter of weeks.
Another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta®), has not fared as well as tisagenlecleucel. The National Institute for Health and Care Excellence (NICE) recently issued a draft guidance recommending against the use of axicabtagene ciloleucel in England.
Axicabtagene ciloleucel was approved by the EC to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. NICE also said the price of axicabtagene ciloleucel is too high for the therapy to be considered a cost-effective use of NHS resources, and axicabtagene ciloleucel does not meet the criteria for inclusion in the Cancer Drugs Fund.
The National Health Service (NHS) of England has announced that tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy, will soon be available for certain leukemia patients.
Tisagenlecleucel will be made available through the Cancer Drugs Fund, and patients could potentially begin receiving the treatment within weeks.
NHS England struck a deal with Novartis to lower the price of tisagenlecleucel, which costs around £282,000 per patient at its full list price. The discount offered to the NHS is confidential.
Tisagenlecleucel was recently approved by the European Commission (EC) to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.
The EC also approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
However, tisagenlecleucel will only be available for ALL patients in England, at least initially. A decision has not been made regarding funding for tisagenlecleucel in DLBCL, and Novartis previously decided to launch tisagenlecleucel in ALL first.
“It’s fantastic news for children and young people with this form of leukemia that CAR T-cell therapy will be made available on the NHS, making them the first in Europe to have routine access to this exciting new type of immunotherapy,” said Charles Swanton, Cancer Research UK’s chief clinician.
The first three NHS hospitals to go through the international accreditation process for the provision of tisagenlecleucel are in London, Manchester, and Newcastle. Subject to passing accreditation requirements, the first treatments could begin in a matter of weeks.
Another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta®), has not fared as well as tisagenlecleucel. The National Institute for Health and Care Excellence (NICE) recently issued a draft guidance recommending against the use of axicabtagene ciloleucel in England.
Axicabtagene ciloleucel was approved by the EC to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. NICE also said the price of axicabtagene ciloleucel is too high for the therapy to be considered a cost-effective use of NHS resources, and axicabtagene ciloleucel does not meet the criteria for inclusion in the Cancer Drugs Fund.
The National Health Service (NHS) of England has announced that tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy, will soon be available for certain leukemia patients.
Tisagenlecleucel will be made available through the Cancer Drugs Fund, and patients could potentially begin receiving the treatment within weeks.
NHS England struck a deal with Novartis to lower the price of tisagenlecleucel, which costs around £282,000 per patient at its full list price. The discount offered to the NHS is confidential.
Tisagenlecleucel was recently approved by the European Commission (EC) to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.
The EC also approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
However, tisagenlecleucel will only be available for ALL patients in England, at least initially. A decision has not been made regarding funding for tisagenlecleucel in DLBCL, and Novartis previously decided to launch tisagenlecleucel in ALL first.
“It’s fantastic news for children and young people with this form of leukemia that CAR T-cell therapy will be made available on the NHS, making them the first in Europe to have routine access to this exciting new type of immunotherapy,” said Charles Swanton, Cancer Research UK’s chief clinician.
The first three NHS hospitals to go through the international accreditation process for the provision of tisagenlecleucel are in London, Manchester, and Newcastle. Subject to passing accreditation requirements, the first treatments could begin in a matter of weeks.
Another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta®), has not fared as well as tisagenlecleucel. The National Institute for Health and Care Excellence (NICE) recently issued a draft guidance recommending against the use of axicabtagene ciloleucel in England.
Axicabtagene ciloleucel was approved by the EC to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. NICE also said the price of axicabtagene ciloleucel is too high for the therapy to be considered a cost-effective use of NHS resources, and axicabtagene ciloleucel does not meet the criteria for inclusion in the Cancer Drugs Fund.
Single-dose influenza drug baloxavir similar to oseltamivir in efficacy
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Single-dose influenza antiviral baloxavir shows efficacy similar to that of oseltamivir.
Major finding: Baloxavir shows similar time to alleviation of influenza symptoms compared with oseltamivir, but greater reductions in viral load.
Study details: Phase 2 and phase 3 randomized controlled trials in 389 and 1,366 otherwise healthy patients with influenza.
Disclosures: The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
Source: Hayden F et al. N Engl J Med 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
Community-based therapy improved asthma outcomes in African American teens
, according to results published in Pediatrics.
In a study of 167 African American patients aged 12-16 years, the 84 randomly assigned to Multisystemic Therapy–Health Care (MST-HC) had greater improvement in forced expiratory volume in 1 second (FEV1) over time, compared with the 83 patients randomly assigned to family support (FS) therapy (beta = 0.097, t[164.27] = 2.52; P = .01). Improvements in secondary outcomes also were observed in this group, reported Sylvie Naar, PhD, of Florida State University, Tallahassee, and her coauthors.
They studied African American adolescents with moderate to severe persistent asthma who resided in a home setting with a caregiver and were at high risk for poorly controlled asthma. Families were randomized to either MST-HC (84 patients) or FS (83 patients) based on severity of urgent care use, and follow-up was completed 7 and 12 months after baseline assessment. Families were paid $50 for each assessment.
FEV1 was the primary outcome. Secondary outcomes were medication adherence, symptom severity and frequency, inpatient hospitalizations, and ED visits. Medication adherence was evaluated via the Family Asthma Management System Scale (FAMSS) and the Daily Phone Diary (DPD). Other outcomes were confirmed via medical records.
Patients in the FS control group received weekly home-based counseling for up to 6 months. Patients in the MST-HC treatment group were first engaged in a motivational session with a therapist and evaluated for asthma management with interviews and observations within the home and community. Once possible contributing factors to poor asthma management (such as medication underuse or low parental monitoring) were identified, targeted interventions such as skills training, behavioral and family therapy, or communication training with school and medical staff were chosen, and treatment goals continually monitored and modified, the authors said.
The mean length of treatment until termination in the MST-HC group was 5 months, and the mean number of sessions was 27. In the FS group, mean length of treatment was 4 months, and the mean number of sessions was 11.
FEV1 for the MST-HC group improved from 2.05 at baseline to 2.25 at 7 months (a 10% improvement), and to 2.37 (a 16% improvement) at 12 months, compared with an improvement from 2.21 to 2.31 at 7 months (a 4% improvement) and 2.33 (a 5% improvement) at 12 months in the control group, the authors reported.
At 12 months, FAMSS adherence scores improved from 4.19 to 5.24 in the MST-HC group and from 4.61 to 4.72 in the control group.
DPD adherence scores improved from a mean of 0.33 at baseline to 0.69 for the MST-HC group, and from 0.43 to 0.46 in the FS group.
At 12 months, the mean frequency of asthma symptoms in the MST-HC group improved from 2.75 at baseline to 1.43, compared with a decline of 2.67 to 2.58 in the control group. The mean number of hospitalizations in the MST-HC group improved from 0.87 to 0.24, compared with a change from 0.66 to 0.34 in the control group.
The study results are “especially noteworthy because African American adolescents experience greater morbidity and mortality from asthma than white adolescents even when controlling for socioeconomic variables,” Dr. Naar and her associates wrote. Future research should focus on the “transportability” of MST-HC treatment to community settings, which is “ready to be studied in effectiveness and implementation trials.”
The study was supported by a National Institutes of Health grant. Coauthor Phillippe Cunningham, PhD, is a co-owner of Evidence-Based Services, a network partner organization that is licensed to disseminate Multisystemic Therapy for drug court and juvenile delinquency settings. The other authors said they have no potential conflicts of interest.
SOURCE: Naar S et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3737.
, according to results published in Pediatrics.
In a study of 167 African American patients aged 12-16 years, the 84 randomly assigned to Multisystemic Therapy–Health Care (MST-HC) had greater improvement in forced expiratory volume in 1 second (FEV1) over time, compared with the 83 patients randomly assigned to family support (FS) therapy (beta = 0.097, t[164.27] = 2.52; P = .01). Improvements in secondary outcomes also were observed in this group, reported Sylvie Naar, PhD, of Florida State University, Tallahassee, and her coauthors.
They studied African American adolescents with moderate to severe persistent asthma who resided in a home setting with a caregiver and were at high risk for poorly controlled asthma. Families were randomized to either MST-HC (84 patients) or FS (83 patients) based on severity of urgent care use, and follow-up was completed 7 and 12 months after baseline assessment. Families were paid $50 for each assessment.
FEV1 was the primary outcome. Secondary outcomes were medication adherence, symptom severity and frequency, inpatient hospitalizations, and ED visits. Medication adherence was evaluated via the Family Asthma Management System Scale (FAMSS) and the Daily Phone Diary (DPD). Other outcomes were confirmed via medical records.
Patients in the FS control group received weekly home-based counseling for up to 6 months. Patients in the MST-HC treatment group were first engaged in a motivational session with a therapist and evaluated for asthma management with interviews and observations within the home and community. Once possible contributing factors to poor asthma management (such as medication underuse or low parental monitoring) were identified, targeted interventions such as skills training, behavioral and family therapy, or communication training with school and medical staff were chosen, and treatment goals continually monitored and modified, the authors said.
The mean length of treatment until termination in the MST-HC group was 5 months, and the mean number of sessions was 27. In the FS group, mean length of treatment was 4 months, and the mean number of sessions was 11.
FEV1 for the MST-HC group improved from 2.05 at baseline to 2.25 at 7 months (a 10% improvement), and to 2.37 (a 16% improvement) at 12 months, compared with an improvement from 2.21 to 2.31 at 7 months (a 4% improvement) and 2.33 (a 5% improvement) at 12 months in the control group, the authors reported.
At 12 months, FAMSS adherence scores improved from 4.19 to 5.24 in the MST-HC group and from 4.61 to 4.72 in the control group.
DPD adherence scores improved from a mean of 0.33 at baseline to 0.69 for the MST-HC group, and from 0.43 to 0.46 in the FS group.
At 12 months, the mean frequency of asthma symptoms in the MST-HC group improved from 2.75 at baseline to 1.43, compared with a decline of 2.67 to 2.58 in the control group. The mean number of hospitalizations in the MST-HC group improved from 0.87 to 0.24, compared with a change from 0.66 to 0.34 in the control group.
The study results are “especially noteworthy because African American adolescents experience greater morbidity and mortality from asthma than white adolescents even when controlling for socioeconomic variables,” Dr. Naar and her associates wrote. Future research should focus on the “transportability” of MST-HC treatment to community settings, which is “ready to be studied in effectiveness and implementation trials.”
The study was supported by a National Institutes of Health grant. Coauthor Phillippe Cunningham, PhD, is a co-owner of Evidence-Based Services, a network partner organization that is licensed to disseminate Multisystemic Therapy for drug court and juvenile delinquency settings. The other authors said they have no potential conflicts of interest.
SOURCE: Naar S et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3737.
, according to results published in Pediatrics.
In a study of 167 African American patients aged 12-16 years, the 84 randomly assigned to Multisystemic Therapy–Health Care (MST-HC) had greater improvement in forced expiratory volume in 1 second (FEV1) over time, compared with the 83 patients randomly assigned to family support (FS) therapy (beta = 0.097, t[164.27] = 2.52; P = .01). Improvements in secondary outcomes also were observed in this group, reported Sylvie Naar, PhD, of Florida State University, Tallahassee, and her coauthors.
They studied African American adolescents with moderate to severe persistent asthma who resided in a home setting with a caregiver and were at high risk for poorly controlled asthma. Families were randomized to either MST-HC (84 patients) or FS (83 patients) based on severity of urgent care use, and follow-up was completed 7 and 12 months after baseline assessment. Families were paid $50 for each assessment.
FEV1 was the primary outcome. Secondary outcomes were medication adherence, symptom severity and frequency, inpatient hospitalizations, and ED visits. Medication adherence was evaluated via the Family Asthma Management System Scale (FAMSS) and the Daily Phone Diary (DPD). Other outcomes were confirmed via medical records.
Patients in the FS control group received weekly home-based counseling for up to 6 months. Patients in the MST-HC treatment group were first engaged in a motivational session with a therapist and evaluated for asthma management with interviews and observations within the home and community. Once possible contributing factors to poor asthma management (such as medication underuse or low parental monitoring) were identified, targeted interventions such as skills training, behavioral and family therapy, or communication training with school and medical staff were chosen, and treatment goals continually monitored and modified, the authors said.
The mean length of treatment until termination in the MST-HC group was 5 months, and the mean number of sessions was 27. In the FS group, mean length of treatment was 4 months, and the mean number of sessions was 11.
FEV1 for the MST-HC group improved from 2.05 at baseline to 2.25 at 7 months (a 10% improvement), and to 2.37 (a 16% improvement) at 12 months, compared with an improvement from 2.21 to 2.31 at 7 months (a 4% improvement) and 2.33 (a 5% improvement) at 12 months in the control group, the authors reported.
At 12 months, FAMSS adherence scores improved from 4.19 to 5.24 in the MST-HC group and from 4.61 to 4.72 in the control group.
DPD adherence scores improved from a mean of 0.33 at baseline to 0.69 for the MST-HC group, and from 0.43 to 0.46 in the FS group.
At 12 months, the mean frequency of asthma symptoms in the MST-HC group improved from 2.75 at baseline to 1.43, compared with a decline of 2.67 to 2.58 in the control group. The mean number of hospitalizations in the MST-HC group improved from 0.87 to 0.24, compared with a change from 0.66 to 0.34 in the control group.
The study results are “especially noteworthy because African American adolescents experience greater morbidity and mortality from asthma than white adolescents even when controlling for socioeconomic variables,” Dr. Naar and her associates wrote. Future research should focus on the “transportability” of MST-HC treatment to community settings, which is “ready to be studied in effectiveness and implementation trials.”
The study was supported by a National Institutes of Health grant. Coauthor Phillippe Cunningham, PhD, is a co-owner of Evidence-Based Services, a network partner organization that is licensed to disseminate Multisystemic Therapy for drug court and juvenile delinquency settings. The other authors said they have no potential conflicts of interest.
SOURCE: Naar S et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3737.
FROM PEDIATRICS
Key clinical point: Multisystemic Therapy–Health Care (MST-HC) significantly improved outcomes in African American adolescents with moderate to severe asthma.
Major finding: Patients randomly assigned to MST-HC treatment had greater improvement in FEV1 over time, compared with controls (beta = 0.097; t(164.27) = 2.52; P = .01).
Study details: A study of 167 African American patients aged 12-16 years, randomly assigned to either MST-HC or FS.
Disclosures: The study was supported by a National Institutes of Health grant. Coauthor Phillippe Cunningham, PhD, is a co-owner of Evidence-Based Services, a network partner organization that is licensed to disseminate multisystemic therapy for drug court and juvenile delinquency settings. The other authors said they have no potential conflicts of interest.
Source: Naar S et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3737.
Over past 20 years, the percentage of children with ADHD nearly doubles
The number of children diagnosed with ADHD has reached more than 10%, a significant increase during the past 20 years, according to a recent study in JAMA.
The rise was most pronounced in minority groups, suggesting that better access to health insurance and mental health treatment through the Affordable Care Act might have played some role in the increase. The rate of diagnosis during that time period doubled in girls, although it was still much lower than in boys.
But the researchers say they found no evidence confirming frequent complaints that the condition is overdiagnosed or misdiagnosed.
The United States has significantly more instances of ADHD than do other developed countries, which researchers said has led some to think Americans are overdiagnosing children. Wei Bao, MD, PhD, lead author of the study, said in an interview that a review of studies around the world does not support that.
”I don’t think overdiagnosis is the main issue,” he said.
Nonetheless, those doubts persist. Stephen Hinshaw, MD, who coauthored a 2014 book called “The ADHD Explosion: Myths, Medication, Money, and Today’s Push for Performance,” compared ADHD with depression. He said in an interview that neither condition has unequivocal biological markers, which makes it hard to determine if a patient truly has the condition without lengthy psychological evaluations. Symptoms of ADHD can include inattention, fidgety behavior, and impulsivity.
“It’s probably not a true epidemic of ADHD,” said Dr. Hinshaw, a professor of psychology at the University of California, Berkeley, and a professor of psychiatry at University of California, San Francisco. “It might be an epidemic of diagnosing it.”
In interpreting their results, however, the study’s authors tied the higher numbers to better understanding of the condition by doctors and the public, new standards for diagnosis and an increase in access to health insurance through the ACA.
Because of the ACA, “some low-income families have improved access to services and referrals,” said Dr. Bao, an epidemiologist at the University of Iowa College of Public Health in Iowa City.
The study, published in JAMA Network Open, used data from the National Health Interview Survey, an annual federal survey of about 35,000 households. It found a steady increase in diagnoses in children from about 6% during 1997-1998 to more than 10% during 2015-2016.
Advances in medical technology also may have contributed to the increase, according to the research. Twenty years ago, preterm or low-birth-weight babies had a harder time surviving. Those factors increase the risk of being diagnosed with ADHD.
The study also suggests that fewer stigmas about mental health care in minority communities also may lead to more people receiving an ADHD diagnosis.
In the late 1990s, 7.2% of non-Hispanic white children, 4.7% of non-Hispanic black children, and 3.6% of Hispanic children were diagnosed with ADHD, according to the study. By 2016, it was 12% of white kids, 12.8% of blacks, and 6.1% of Hispanics.
Over the past several decades, Dr. Hinshaw said, there’s been an expanded view of who can develop ADHD. It’s no longer viewed as a disease that affects only white middle-class boys, as eating disorders are no longer seen as afflicting only white middle-class girls.
Still, he cautioned against overdiagnosing ADHD in communities in which behavioral issues could be the result of social or environmental factors such as overcrowded classrooms.
The study found rates of ADHD among girls rose from 3% to more than 6% over the study period. It said that was partly a result of a change in how the condition is classified. For years, ADHD pertained to children who were hyperactive. But in recent years, the American Psychiatric Association added to its guide of mental health conditions that diagnosis should also include some children who are inattentive, Dr. Bao said. That raised the number of girls, he explained, because it seems they are more likely to be in that second subtype.
“If we compare these two, you can easily imagine people will easily recognize hyperactivity,” he said.
That rang true for Ruth Hay, a 25-year-old student and cook from New York who now lives in Jerusalem. She was diagnosed with what was then called ADD the summer between second and third grade.
Ms. Hay said her hyperactive tendencies aren’t as “loud” as some people’s. She’s less likely to bounce around a room than she is to bounce in her chair, she said.
Yet, despite her early diagnosis, Ms. Hay said, no one ever told her about other symptoms. For example, she said, she suffers from executive dysfunction, which leaves her feeling unable to accomplish tasks, no matter how much she wanted to or tried.
“I grew up being called lazy in periods of time when I wasn’t,” Ms. Hay said. “If you look at a list of all the various ADHD symptoms, I have all of them to one degree or another, but the only ones ever discussed with me was you might be less focused and more fidgety.”
“I don’t know how my brain would be if I didn’t have it,” she added. “I don’t know if I’d still be me, but all it has been for me is a disability.”
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation.
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
The number of children diagnosed with ADHD has reached more than 10%, a significant increase during the past 20 years, according to a recent study in JAMA.
The rise was most pronounced in minority groups, suggesting that better access to health insurance and mental health treatment through the Affordable Care Act might have played some role in the increase. The rate of diagnosis during that time period doubled in girls, although it was still much lower than in boys.
But the researchers say they found no evidence confirming frequent complaints that the condition is overdiagnosed or misdiagnosed.
The United States has significantly more instances of ADHD than do other developed countries, which researchers said has led some to think Americans are overdiagnosing children. Wei Bao, MD, PhD, lead author of the study, said in an interview that a review of studies around the world does not support that.
”I don’t think overdiagnosis is the main issue,” he said.
Nonetheless, those doubts persist. Stephen Hinshaw, MD, who coauthored a 2014 book called “The ADHD Explosion: Myths, Medication, Money, and Today’s Push for Performance,” compared ADHD with depression. He said in an interview that neither condition has unequivocal biological markers, which makes it hard to determine if a patient truly has the condition without lengthy psychological evaluations. Symptoms of ADHD can include inattention, fidgety behavior, and impulsivity.
“It’s probably not a true epidemic of ADHD,” said Dr. Hinshaw, a professor of psychology at the University of California, Berkeley, and a professor of psychiatry at University of California, San Francisco. “It might be an epidemic of diagnosing it.”
In interpreting their results, however, the study’s authors tied the higher numbers to better understanding of the condition by doctors and the public, new standards for diagnosis and an increase in access to health insurance through the ACA.
Because of the ACA, “some low-income families have improved access to services and referrals,” said Dr. Bao, an epidemiologist at the University of Iowa College of Public Health in Iowa City.
The study, published in JAMA Network Open, used data from the National Health Interview Survey, an annual federal survey of about 35,000 households. It found a steady increase in diagnoses in children from about 6% during 1997-1998 to more than 10% during 2015-2016.
Advances in medical technology also may have contributed to the increase, according to the research. Twenty years ago, preterm or low-birth-weight babies had a harder time surviving. Those factors increase the risk of being diagnosed with ADHD.
The study also suggests that fewer stigmas about mental health care in minority communities also may lead to more people receiving an ADHD diagnosis.
In the late 1990s, 7.2% of non-Hispanic white children, 4.7% of non-Hispanic black children, and 3.6% of Hispanic children were diagnosed with ADHD, according to the study. By 2016, it was 12% of white kids, 12.8% of blacks, and 6.1% of Hispanics.
Over the past several decades, Dr. Hinshaw said, there’s been an expanded view of who can develop ADHD. It’s no longer viewed as a disease that affects only white middle-class boys, as eating disorders are no longer seen as afflicting only white middle-class girls.
Still, he cautioned against overdiagnosing ADHD in communities in which behavioral issues could be the result of social or environmental factors such as overcrowded classrooms.
The study found rates of ADHD among girls rose from 3% to more than 6% over the study period. It said that was partly a result of a change in how the condition is classified. For years, ADHD pertained to children who were hyperactive. But in recent years, the American Psychiatric Association added to its guide of mental health conditions that diagnosis should also include some children who are inattentive, Dr. Bao said. That raised the number of girls, he explained, because it seems they are more likely to be in that second subtype.
“If we compare these two, you can easily imagine people will easily recognize hyperactivity,” he said.
That rang true for Ruth Hay, a 25-year-old student and cook from New York who now lives in Jerusalem. She was diagnosed with what was then called ADD the summer between second and third grade.
Ms. Hay said her hyperactive tendencies aren’t as “loud” as some people’s. She’s less likely to bounce around a room than she is to bounce in her chair, she said.
Yet, despite her early diagnosis, Ms. Hay said, no one ever told her about other symptoms. For example, she said, she suffers from executive dysfunction, which leaves her feeling unable to accomplish tasks, no matter how much she wanted to or tried.
“I grew up being called lazy in periods of time when I wasn’t,” Ms. Hay said. “If you look at a list of all the various ADHD symptoms, I have all of them to one degree or another, but the only ones ever discussed with me was you might be less focused and more fidgety.”
“I don’t know how my brain would be if I didn’t have it,” she added. “I don’t know if I’d still be me, but all it has been for me is a disability.”
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation.
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
The number of children diagnosed with ADHD has reached more than 10%, a significant increase during the past 20 years, according to a recent study in JAMA.
The rise was most pronounced in minority groups, suggesting that better access to health insurance and mental health treatment through the Affordable Care Act might have played some role in the increase. The rate of diagnosis during that time period doubled in girls, although it was still much lower than in boys.
But the researchers say they found no evidence confirming frequent complaints that the condition is overdiagnosed or misdiagnosed.
The United States has significantly more instances of ADHD than do other developed countries, which researchers said has led some to think Americans are overdiagnosing children. Wei Bao, MD, PhD, lead author of the study, said in an interview that a review of studies around the world does not support that.
”I don’t think overdiagnosis is the main issue,” he said.
Nonetheless, those doubts persist. Stephen Hinshaw, MD, who coauthored a 2014 book called “The ADHD Explosion: Myths, Medication, Money, and Today’s Push for Performance,” compared ADHD with depression. He said in an interview that neither condition has unequivocal biological markers, which makes it hard to determine if a patient truly has the condition without lengthy psychological evaluations. Symptoms of ADHD can include inattention, fidgety behavior, and impulsivity.
“It’s probably not a true epidemic of ADHD,” said Dr. Hinshaw, a professor of psychology at the University of California, Berkeley, and a professor of psychiatry at University of California, San Francisco. “It might be an epidemic of diagnosing it.”
In interpreting their results, however, the study’s authors tied the higher numbers to better understanding of the condition by doctors and the public, new standards for diagnosis and an increase in access to health insurance through the ACA.
Because of the ACA, “some low-income families have improved access to services and referrals,” said Dr. Bao, an epidemiologist at the University of Iowa College of Public Health in Iowa City.
The study, published in JAMA Network Open, used data from the National Health Interview Survey, an annual federal survey of about 35,000 households. It found a steady increase in diagnoses in children from about 6% during 1997-1998 to more than 10% during 2015-2016.
Advances in medical technology also may have contributed to the increase, according to the research. Twenty years ago, preterm or low-birth-weight babies had a harder time surviving. Those factors increase the risk of being diagnosed with ADHD.
The study also suggests that fewer stigmas about mental health care in minority communities also may lead to more people receiving an ADHD diagnosis.
In the late 1990s, 7.2% of non-Hispanic white children, 4.7% of non-Hispanic black children, and 3.6% of Hispanic children were diagnosed with ADHD, according to the study. By 2016, it was 12% of white kids, 12.8% of blacks, and 6.1% of Hispanics.
Over the past several decades, Dr. Hinshaw said, there’s been an expanded view of who can develop ADHD. It’s no longer viewed as a disease that affects only white middle-class boys, as eating disorders are no longer seen as afflicting only white middle-class girls.
Still, he cautioned against overdiagnosing ADHD in communities in which behavioral issues could be the result of social or environmental factors such as overcrowded classrooms.
The study found rates of ADHD among girls rose from 3% to more than 6% over the study period. It said that was partly a result of a change in how the condition is classified. For years, ADHD pertained to children who were hyperactive. But in recent years, the American Psychiatric Association added to its guide of mental health conditions that diagnosis should also include some children who are inattentive, Dr. Bao said. That raised the number of girls, he explained, because it seems they are more likely to be in that second subtype.
“If we compare these two, you can easily imagine people will easily recognize hyperactivity,” he said.
That rang true for Ruth Hay, a 25-year-old student and cook from New York who now lives in Jerusalem. She was diagnosed with what was then called ADD the summer between second and third grade.
Ms. Hay said her hyperactive tendencies aren’t as “loud” as some people’s. She’s less likely to bounce around a room than she is to bounce in her chair, she said.
Yet, despite her early diagnosis, Ms. Hay said, no one ever told her about other symptoms. For example, she said, she suffers from executive dysfunction, which leaves her feeling unable to accomplish tasks, no matter how much she wanted to or tried.
“I grew up being called lazy in periods of time when I wasn’t,” Ms. Hay said. “If you look at a list of all the various ADHD symptoms, I have all of them to one degree or another, but the only ones ever discussed with me was you might be less focused and more fidgety.”
“I don’t know how my brain would be if I didn’t have it,” she added. “I don’t know if I’d still be me, but all it has been for me is a disability.”
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation.
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.