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Healthy gut tied to better cognition
Investigators conducted cognitive testing and analyzed stool samples in close to 600 adults and found that beta-diversity, which is a between-person measure of gut microbial community composition, was significantly associated with cognitive scores.
Three specific bacterial genera showed a positive association with performance on at least one cognitive test, while one showed a negative association.
“Data from our study support an association between the gut microbial community and measure of cognitive function – results that are consistent with findings from other human and animal research,” study investigator Katie Meyer, ScD, assistant professor, department of nutrition, UNC Gillings School of Public Health, Chapel Hill, N.C., told this news organization.
“However, it is also important to recognize that we are still learning about how to characterize the role of this dynamic ecological community and delineate mechanistic pathways,” she said.
The study was published online Feb 8 in JAMA Network Open.
‘Novel’ research
“Communication pathways between gut bacteria and neurologic function (referred to as the ‘gut-brain axis’) have emerged as a novel area of research into potential mechanisms regulating brain health through immunologic, metabolic, and endocrine pathways,” the authors wrote.
A number of studies have “shown associations between gut microbial measures and neurological outcomes, including cognitive function and dementia,” but mechanisms underlying these associations “have not been fully established.”
Animal and small-scale human studies have suggested that reduced microbial diversity is associated with poorer cognition, but studies have not been conducted in community-based large and diverse populations.
The researchers therefore examined cross-sectional associations of gut microbial diversity and taxonomic composition with cognitive status in a large group of community-dwelling, sociodemographically diverse Black and White adults living in four metropolitan areas who were participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
They hypothesized that microbial diversity would be positively associated with global as well as domain-specific cognitive status and that higher cognitive status would be associated with specific taxonomic groups involved in short-chain fatty acid production.
The CARDIA’s year 30 follow-up examination took place during 2015-2016, when the original participants ranged in age from 48 to 60 years. During that examination, participants took a battery of cognitive assessments, and 615 also provided a stool sample for a microbiome substudy; of these, 597 (mean [SD] age, 55.2 [3.5] years, 44.7% Black, 45.2% White) had both stool DNA available for sequencing and a complete complement of cognitive tests and were included in the current study.
The cognitive tests included the Digit Symbol Substitution Test (DSST); Rey-Auditory Verbal Learning Test (RAVLT); the timed Stroop test; letter fluency and category fluency; and the Montreal Cognitive Assessment (MoCA).
Covariates that might confound associations between microbial and cognitive measures, including body mass index, diabetes, age, sex, race, field center, education, physical activity, current smoking, diet quality, number of medications, and hypertension, were included in the analyses.
The investigators conducted three standard microbial analyses: within-person alpha-diversity; between-person beta-diversity; and individual taxa.
Potential pathways
The strongest associations in the variance tests for beta-diversity, which were significant for all cognition measures in multivariable-adjusted principal coordinates analysis (all Ps = .001 except for the Stroop, which was .007). However, the association with letter fluency was not deemed significant (P = .07).
After fully adjusting for sociodemographic variables, health behaviors, and clinical covariates, the researchers found that three genera were positively associated, while one was negatively associated with cognitive measures.
“The strongest results from our study were from a multivariate analysis that can be considered a test of the overall community,” said Dr. Meyer.
She pointed to several pathways through which gut microbiota can contribute to brain health.
“We know from mechanistic studies in animal models that the gut microbiota is involved in systemic inflammation, which is a risk factor for brain pathology,” she said.
Moreover, “the gut microbiota is involved in the production of metabolites that may impact the brain, including tryptophan metabolites and short-chain fatty acids, many of which derive from dietary components, which may help explain associations between diet and cognition (e.g., the Mediterranean-style diet can be protective),” she added.
Starting point
Commenting for this news organization, Timothy Dinan, MD, PhD, professor of psychiatry and an investigator, APC Microbiome Institute, University College Cork, Ireland, said, “This is an important study, adding to the growing body of evidence that gut microbes influence brain function.”
Dr. Dinan, who was not involved with the study, continued: “In an impressively large sample, an association between cognition and gut microbiota architecture was demonstrated.”
He cautioned that the study “is limited by the fact that it is cross-sectional, and the relationships are correlational.” Nevertheless, “despite these obvious caveats, the paper undoubtedly advances the field.”
Dr. Meyer agreed, noting that there is “a paucity of biomarkers that can be used to predict cognitive decline and dementia,” but because their study was cross-sectional, “we cannot assess temporality (i.e., whether gut microbiota predicts cognitive decline); but, as a start, we can assess associations.”
She added that “at this point, we know far more about modifiable risk factors that have been shown to be positively associated with cognitive function,” including eating a Mediterranean diet and engaging in physical activity.
“It is possible that protective effects of diet and activity may, in part, operate thorough the gut microbiota,” Dr. Meyer suggested.
The CARDIA study is supported by the National Heart, Lung, and Blood Institute, the Intramural Research Program of the National Institute on Aging, and the University of North Carolina Nutrition Research Institute. Dr. Meyer and coauthors and Dr. Dinan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators conducted cognitive testing and analyzed stool samples in close to 600 adults and found that beta-diversity, which is a between-person measure of gut microbial community composition, was significantly associated with cognitive scores.
Three specific bacterial genera showed a positive association with performance on at least one cognitive test, while one showed a negative association.
“Data from our study support an association between the gut microbial community and measure of cognitive function – results that are consistent with findings from other human and animal research,” study investigator Katie Meyer, ScD, assistant professor, department of nutrition, UNC Gillings School of Public Health, Chapel Hill, N.C., told this news organization.
“However, it is also important to recognize that we are still learning about how to characterize the role of this dynamic ecological community and delineate mechanistic pathways,” she said.
The study was published online Feb 8 in JAMA Network Open.
‘Novel’ research
“Communication pathways between gut bacteria and neurologic function (referred to as the ‘gut-brain axis’) have emerged as a novel area of research into potential mechanisms regulating brain health through immunologic, metabolic, and endocrine pathways,” the authors wrote.
A number of studies have “shown associations between gut microbial measures and neurological outcomes, including cognitive function and dementia,” but mechanisms underlying these associations “have not been fully established.”
Animal and small-scale human studies have suggested that reduced microbial diversity is associated with poorer cognition, but studies have not been conducted in community-based large and diverse populations.
The researchers therefore examined cross-sectional associations of gut microbial diversity and taxonomic composition with cognitive status in a large group of community-dwelling, sociodemographically diverse Black and White adults living in four metropolitan areas who were participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
They hypothesized that microbial diversity would be positively associated with global as well as domain-specific cognitive status and that higher cognitive status would be associated with specific taxonomic groups involved in short-chain fatty acid production.
The CARDIA’s year 30 follow-up examination took place during 2015-2016, when the original participants ranged in age from 48 to 60 years. During that examination, participants took a battery of cognitive assessments, and 615 also provided a stool sample for a microbiome substudy; of these, 597 (mean [SD] age, 55.2 [3.5] years, 44.7% Black, 45.2% White) had both stool DNA available for sequencing and a complete complement of cognitive tests and were included in the current study.
The cognitive tests included the Digit Symbol Substitution Test (DSST); Rey-Auditory Verbal Learning Test (RAVLT); the timed Stroop test; letter fluency and category fluency; and the Montreal Cognitive Assessment (MoCA).
Covariates that might confound associations between microbial and cognitive measures, including body mass index, diabetes, age, sex, race, field center, education, physical activity, current smoking, diet quality, number of medications, and hypertension, were included in the analyses.
The investigators conducted three standard microbial analyses: within-person alpha-diversity; between-person beta-diversity; and individual taxa.
Potential pathways
The strongest associations in the variance tests for beta-diversity, which were significant for all cognition measures in multivariable-adjusted principal coordinates analysis (all Ps = .001 except for the Stroop, which was .007). However, the association with letter fluency was not deemed significant (P = .07).
After fully adjusting for sociodemographic variables, health behaviors, and clinical covariates, the researchers found that three genera were positively associated, while one was negatively associated with cognitive measures.
“The strongest results from our study were from a multivariate analysis that can be considered a test of the overall community,” said Dr. Meyer.
She pointed to several pathways through which gut microbiota can contribute to brain health.
“We know from mechanistic studies in animal models that the gut microbiota is involved in systemic inflammation, which is a risk factor for brain pathology,” she said.
Moreover, “the gut microbiota is involved in the production of metabolites that may impact the brain, including tryptophan metabolites and short-chain fatty acids, many of which derive from dietary components, which may help explain associations between diet and cognition (e.g., the Mediterranean-style diet can be protective),” she added.
Starting point
Commenting for this news organization, Timothy Dinan, MD, PhD, professor of psychiatry and an investigator, APC Microbiome Institute, University College Cork, Ireland, said, “This is an important study, adding to the growing body of evidence that gut microbes influence brain function.”
Dr. Dinan, who was not involved with the study, continued: “In an impressively large sample, an association between cognition and gut microbiota architecture was demonstrated.”
He cautioned that the study “is limited by the fact that it is cross-sectional, and the relationships are correlational.” Nevertheless, “despite these obvious caveats, the paper undoubtedly advances the field.”
Dr. Meyer agreed, noting that there is “a paucity of biomarkers that can be used to predict cognitive decline and dementia,” but because their study was cross-sectional, “we cannot assess temporality (i.e., whether gut microbiota predicts cognitive decline); but, as a start, we can assess associations.”
She added that “at this point, we know far more about modifiable risk factors that have been shown to be positively associated with cognitive function,” including eating a Mediterranean diet and engaging in physical activity.
“It is possible that protective effects of diet and activity may, in part, operate thorough the gut microbiota,” Dr. Meyer suggested.
The CARDIA study is supported by the National Heart, Lung, and Blood Institute, the Intramural Research Program of the National Institute on Aging, and the University of North Carolina Nutrition Research Institute. Dr. Meyer and coauthors and Dr. Dinan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators conducted cognitive testing and analyzed stool samples in close to 600 adults and found that beta-diversity, which is a between-person measure of gut microbial community composition, was significantly associated with cognitive scores.
Three specific bacterial genera showed a positive association with performance on at least one cognitive test, while one showed a negative association.
“Data from our study support an association between the gut microbial community and measure of cognitive function – results that are consistent with findings from other human and animal research,” study investigator Katie Meyer, ScD, assistant professor, department of nutrition, UNC Gillings School of Public Health, Chapel Hill, N.C., told this news organization.
“However, it is also important to recognize that we are still learning about how to characterize the role of this dynamic ecological community and delineate mechanistic pathways,” she said.
The study was published online Feb 8 in JAMA Network Open.
‘Novel’ research
“Communication pathways between gut bacteria and neurologic function (referred to as the ‘gut-brain axis’) have emerged as a novel area of research into potential mechanisms regulating brain health through immunologic, metabolic, and endocrine pathways,” the authors wrote.
A number of studies have “shown associations between gut microbial measures and neurological outcomes, including cognitive function and dementia,” but mechanisms underlying these associations “have not been fully established.”
Animal and small-scale human studies have suggested that reduced microbial diversity is associated with poorer cognition, but studies have not been conducted in community-based large and diverse populations.
The researchers therefore examined cross-sectional associations of gut microbial diversity and taxonomic composition with cognitive status in a large group of community-dwelling, sociodemographically diverse Black and White adults living in four metropolitan areas who were participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
They hypothesized that microbial diversity would be positively associated with global as well as domain-specific cognitive status and that higher cognitive status would be associated with specific taxonomic groups involved in short-chain fatty acid production.
The CARDIA’s year 30 follow-up examination took place during 2015-2016, when the original participants ranged in age from 48 to 60 years. During that examination, participants took a battery of cognitive assessments, and 615 also provided a stool sample for a microbiome substudy; of these, 597 (mean [SD] age, 55.2 [3.5] years, 44.7% Black, 45.2% White) had both stool DNA available for sequencing and a complete complement of cognitive tests and were included in the current study.
The cognitive tests included the Digit Symbol Substitution Test (DSST); Rey-Auditory Verbal Learning Test (RAVLT); the timed Stroop test; letter fluency and category fluency; and the Montreal Cognitive Assessment (MoCA).
Covariates that might confound associations between microbial and cognitive measures, including body mass index, diabetes, age, sex, race, field center, education, physical activity, current smoking, diet quality, number of medications, and hypertension, were included in the analyses.
The investigators conducted three standard microbial analyses: within-person alpha-diversity; between-person beta-diversity; and individual taxa.
Potential pathways
The strongest associations in the variance tests for beta-diversity, which were significant for all cognition measures in multivariable-adjusted principal coordinates analysis (all Ps = .001 except for the Stroop, which was .007). However, the association with letter fluency was not deemed significant (P = .07).
After fully adjusting for sociodemographic variables, health behaviors, and clinical covariates, the researchers found that three genera were positively associated, while one was negatively associated with cognitive measures.
“The strongest results from our study were from a multivariate analysis that can be considered a test of the overall community,” said Dr. Meyer.
She pointed to several pathways through which gut microbiota can contribute to brain health.
“We know from mechanistic studies in animal models that the gut microbiota is involved in systemic inflammation, which is a risk factor for brain pathology,” she said.
Moreover, “the gut microbiota is involved in the production of metabolites that may impact the brain, including tryptophan metabolites and short-chain fatty acids, many of which derive from dietary components, which may help explain associations between diet and cognition (e.g., the Mediterranean-style diet can be protective),” she added.
Starting point
Commenting for this news organization, Timothy Dinan, MD, PhD, professor of psychiatry and an investigator, APC Microbiome Institute, University College Cork, Ireland, said, “This is an important study, adding to the growing body of evidence that gut microbes influence brain function.”
Dr. Dinan, who was not involved with the study, continued: “In an impressively large sample, an association between cognition and gut microbiota architecture was demonstrated.”
He cautioned that the study “is limited by the fact that it is cross-sectional, and the relationships are correlational.” Nevertheless, “despite these obvious caveats, the paper undoubtedly advances the field.”
Dr. Meyer agreed, noting that there is “a paucity of biomarkers that can be used to predict cognitive decline and dementia,” but because their study was cross-sectional, “we cannot assess temporality (i.e., whether gut microbiota predicts cognitive decline); but, as a start, we can assess associations.”
She added that “at this point, we know far more about modifiable risk factors that have been shown to be positively associated with cognitive function,” including eating a Mediterranean diet and engaging in physical activity.
“It is possible that protective effects of diet and activity may, in part, operate thorough the gut microbiota,” Dr. Meyer suggested.
The CARDIA study is supported by the National Heart, Lung, and Blood Institute, the Intramural Research Program of the National Institute on Aging, and the University of North Carolina Nutrition Research Institute. Dr. Meyer and coauthors and Dr. Dinan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Liquid embolism of AVM tied to high cure rate
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
The migraine-go-round
Any other docs out there have patients on what I call the migraine-go-round?
I first discovered this ride when I started in practice, though back then it was with triptans. You know the game, you’d start someone on one drug because you had samples, or a coupon, or both. A few months later the coupon had run out, and their insurance wouldn’t cover it, so you’d move them to another drug. Maxalt to Imitrex to Zomig to Relpax to Axert to Maxalt.
The ride continued until the majority had gone generic, and I’d almost forgotten about it. You can’t do it with seizure patients or Parkinson’s disease.
But with the advent of the CGRP era, it seems to have started again. Coverage coupons have a limited number of refills, or the deal changes, or a pharmacy stops taking them, or an insurance company changes their mind, or whatever. So we go from Aimovig to Emgality to Qulipta to Ajovy to Nurtec to Aimovig (not necessarily in that order).
It’s annoying (not just for the patients, but for me and my staff as we try to keep up with it), and obviously it doesn’t work for everyone because each patient responds differently. But, if it works, it at least gets some degree of coverage until an insurance company finally approves a given drug for that person. And even then a patient’s own financial circumstances or changing job situation can keep things spinning.
When you finally step off the ride you have to pore back through the chart to figure out which, if any, worked best, or had side effects, or whatever.
A good part of modern medicine is adapting to these sorts of things. Sometimes we have to play the game to get things done.
The trick is learning the rules on the fly – for all involved.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Any other docs out there have patients on what I call the migraine-go-round?
I first discovered this ride when I started in practice, though back then it was with triptans. You know the game, you’d start someone on one drug because you had samples, or a coupon, or both. A few months later the coupon had run out, and their insurance wouldn’t cover it, so you’d move them to another drug. Maxalt to Imitrex to Zomig to Relpax to Axert to Maxalt.
The ride continued until the majority had gone generic, and I’d almost forgotten about it. You can’t do it with seizure patients or Parkinson’s disease.
But with the advent of the CGRP era, it seems to have started again. Coverage coupons have a limited number of refills, or the deal changes, or a pharmacy stops taking them, or an insurance company changes their mind, or whatever. So we go from Aimovig to Emgality to Qulipta to Ajovy to Nurtec to Aimovig (not necessarily in that order).
It’s annoying (not just for the patients, but for me and my staff as we try to keep up with it), and obviously it doesn’t work for everyone because each patient responds differently. But, if it works, it at least gets some degree of coverage until an insurance company finally approves a given drug for that person. And even then a patient’s own financial circumstances or changing job situation can keep things spinning.
When you finally step off the ride you have to pore back through the chart to figure out which, if any, worked best, or had side effects, or whatever.
A good part of modern medicine is adapting to these sorts of things. Sometimes we have to play the game to get things done.
The trick is learning the rules on the fly – for all involved.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Any other docs out there have patients on what I call the migraine-go-round?
I first discovered this ride when I started in practice, though back then it was with triptans. You know the game, you’d start someone on one drug because you had samples, or a coupon, or both. A few months later the coupon had run out, and their insurance wouldn’t cover it, so you’d move them to another drug. Maxalt to Imitrex to Zomig to Relpax to Axert to Maxalt.
The ride continued until the majority had gone generic, and I’d almost forgotten about it. You can’t do it with seizure patients or Parkinson’s disease.
But with the advent of the CGRP era, it seems to have started again. Coverage coupons have a limited number of refills, or the deal changes, or a pharmacy stops taking them, or an insurance company changes their mind, or whatever. So we go from Aimovig to Emgality to Qulipta to Ajovy to Nurtec to Aimovig (not necessarily in that order).
It’s annoying (not just for the patients, but for me and my staff as we try to keep up with it), and obviously it doesn’t work for everyone because each patient responds differently. But, if it works, it at least gets some degree of coverage until an insurance company finally approves a given drug for that person. And even then a patient’s own financial circumstances or changing job situation can keep things spinning.
When you finally step off the ride you have to pore back through the chart to figure out which, if any, worked best, or had side effects, or whatever.
A good part of modern medicine is adapting to these sorts of things. Sometimes we have to play the game to get things done.
The trick is learning the rules on the fly – for all involved.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Alarming rates of self-harm in adults with autism expose a broken system
When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.
Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.
“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.
“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
Falling off a ‘services cliff’
The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.
The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.
Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.
Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.
That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.
The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.
“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
Masking and camouflaging
Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.
“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.
The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.
Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.
Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.
The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.
The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.
The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.
Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
Lightbulb moment?
Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.
“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.
In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.
The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.
“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.
Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.
Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
Scaling the ‘services cliff’
While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.
“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.
Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.
One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.
“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.
Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.
“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”
Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.
Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.
“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.
“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
Falling off a ‘services cliff’
The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.
The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.
Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.
Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.
That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.
The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.
“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
Masking and camouflaging
Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.
“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.
The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.
Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.
Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.
The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.
The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.
The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.
Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
Lightbulb moment?
Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.
“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.
In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.
The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.
“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.
Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.
Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
Scaling the ‘services cliff’
While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.
“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.
Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.
One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.
“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.
Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.
“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”
Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.
Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.
“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.
“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
Falling off a ‘services cliff’
The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.
The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.
Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.
Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.
That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.
The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.
“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
Masking and camouflaging
Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.
“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.
The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.
Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.
Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.
The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.
The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.
The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.
Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
Lightbulb moment?
Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.
“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.
In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.
The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.
“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.
Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.
Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
Scaling the ‘services cliff’
While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.
“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.
Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.
One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.
“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.
Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.
“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”
Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
More evidence links MI to cognitive decline over time
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
New MIS-C guidance addresses diagnostic challenges, cardiac care
Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.
Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.
However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
Update needed in wake of Omicron
“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.
“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.
“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.
“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”
Diagnostic evaluation
The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.
Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
MIS-C and Kawasaki disease phenotypes
Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.
Cardiac management
Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms.
MIS-C treatment
Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.
When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.
The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
COVID-19 and hyperinflammation
The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”
The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.
Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”
The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.
Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.
However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
Update needed in wake of Omicron
“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.
“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.
“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.
“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”
Diagnostic evaluation
The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.
Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
MIS-C and Kawasaki disease phenotypes
Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.
Cardiac management
Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms.
MIS-C treatment
Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.
When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.
The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
COVID-19 and hyperinflammation
The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”
The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.
Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”
The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.
Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.
However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
Update needed in wake of Omicron
“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.
“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.
“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.
“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”
Diagnostic evaluation
The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.
Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
MIS-C and Kawasaki disease phenotypes
Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.
Cardiac management
Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms.
MIS-C treatment
Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.
When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.
The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
COVID-19 and hyperinflammation
The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”
The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.
Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”
The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
FROM ARTHRITIS AND RHEUMATOLOGY
Subvariant may be more dangerous than original Omicron strain
, a lab study from Japan says.
“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.
The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.
“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.
BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.
What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2.
BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote.
“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”
If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.
But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.
“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”
“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.
Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants.
“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”
Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.
It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.
A version of this article first appeared on WebMD.com.
, a lab study from Japan says.
“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.
The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.
“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.
BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.
What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2.
BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote.
“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”
If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.
But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.
“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”
“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.
Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants.
“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”
Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.
It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.
A version of this article first appeared on WebMD.com.
, a lab study from Japan says.
“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.
The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.
“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.
BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.
What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2.
BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote.
“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”
If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.
But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.
“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”
“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.
Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants.
“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”
Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.
It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.
A version of this article first appeared on WebMD.com.
Ivermectin does not stop progression to severe COVID: randomized trial
Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.
“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.
The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.
Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.
Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
Secondary outcomes
Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.
In all the secondary outcomes, there were no significant differences between groups.
Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).
The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
No difference by vaccine status
The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”
Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).
Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.
The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”
Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.
Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.
In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.
Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.
A version of this article first appeared on Medscape.com.
Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.
“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.
The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.
Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.
Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
Secondary outcomes
Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.
In all the secondary outcomes, there were no significant differences between groups.
Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).
The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
No difference by vaccine status
The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”
Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).
Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.
The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”
Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.
Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.
In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.
Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.
A version of this article first appeared on Medscape.com.
Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.
“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.
The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.
Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.
Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
Secondary outcomes
Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.
In all the secondary outcomes, there were no significant differences between groups.
Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).
The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
No difference by vaccine status
The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”
Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).
Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.
The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”
Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.
Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.
In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.
Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.
A version of this article first appeared on Medscape.com.
FROM JAMA INTERNAL MEDICNE
Early in career, female academic docs earn less than males: study
Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.
Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.
Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.
Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.
The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).
Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
Medical schools and hospital leaders have a role to play
The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.
The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.
Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.
“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”
Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”
Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”
In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.
Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.
The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.
A version of this article first appeared on Medscape.com.
Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.
Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.
Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.
Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.
The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).
Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
Medical schools and hospital leaders have a role to play
The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.
The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.
Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.
“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”
Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”
Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”
In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.
Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.
The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.
A version of this article first appeared on Medscape.com.
Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.
Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.
Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.
Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.
The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).
Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
Medical schools and hospital leaders have a role to play
The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.
The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.
Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.
“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”
Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”
Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”
In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.
Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.
The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.
A version of this article first appeared on Medscape.com.
Tenecteplase for stroke thrombolysis up to 24 hours?
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
FROM ISC 2022