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FDA expands oral JAK abrocitinib to adolescents with AD
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Room for improvement in Barrett esophagus care
, an analysis of U.S. registry data shows.
“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.
The study was published online in The American Journal of Gastroenterology.
Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).
Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.
Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.
The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
Study details
Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.
Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.
When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).
Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).
Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).
Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.
The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).
The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.
The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
Practical approaches to improvement
The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”
The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.
Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.
To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.
Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.
“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.
The study had no financial support. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, an analysis of U.S. registry data shows.
“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.
The study was published online in The American Journal of Gastroenterology.
Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).
Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.
Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.
The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
Study details
Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.
Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.
When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).
Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).
Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).
Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.
The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).
The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.
The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
Practical approaches to improvement
The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”
The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.
Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.
To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.
Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.
“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.
The study had no financial support. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, an analysis of U.S. registry data shows.
“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.
The study was published online in The American Journal of Gastroenterology.
Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).
Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.
Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.
The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
Study details
Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.
Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.
When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).
Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).
Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).
Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.
The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).
The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.
The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
Practical approaches to improvement
The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”
The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.
Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.
To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.
Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.
“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.
The study had no financial support. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Differences in brain structure linked to social disadvantage
Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.
Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.
Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.
“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.
“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.
The study was published online in the American Journal of Psychiatry.
‘Toxic stressor’
Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.
Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.
Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.
Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.
Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.
The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”
“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.
“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
A consequence of toxic stress
This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.
The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.
In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”
These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
Social construct?
Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”
Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”
Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.
“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”
These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.
The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.
Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.
Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.
“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.
“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.
The study was published online in the American Journal of Psychiatry.
‘Toxic stressor’
Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.
Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.
Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.
Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.
Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.
The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”
“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.
“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
A consequence of toxic stress
This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.
The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.
In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”
These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
Social construct?
Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”
Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”
Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.
“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”
These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.
The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.
Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.
Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.
“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.
“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.
The study was published online in the American Journal of Psychiatry.
‘Toxic stressor’
Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.
Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.
Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.
Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.
Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.
The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”
“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.
“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
A consequence of toxic stress
This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.
The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.
In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”
These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
Social construct?
Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”
Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”
Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.
“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”
These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.
The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Be aware of hepatic encephalopathy, dementia overlap in older patients with cirrhosis
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Algorithm can spot signs of autism in babies, study says
, a study from Duke University, Durham, N.C., says.
“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.
Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.
“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”
USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.
The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.
“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”
Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.
A version of this article first appeared on WebMD.com.
, a study from Duke University, Durham, N.C., says.
“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.
Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.
“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”
USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.
The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.
“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”
Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.
A version of this article first appeared on WebMD.com.
, a study from Duke University, Durham, N.C., says.
“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.
Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.
“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”
USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.
The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.
“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”
Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.
A version of this article first appeared on WebMD.com.
FROM JAMA NETWORK OPEN
Risk of infections low among kids receiving systemic meds for psoriasis, study finds
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
FROM JAMA DERMATOLOGY
Bright light therapy boosts therapeutic response
Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.
Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.
In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.
The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.
After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.
After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.
“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.
Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.
The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.
However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.
The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.
Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.
Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.
In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.
The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.
After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.
After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.
“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.
Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.
The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.
However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.
The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.
Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.
Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.
In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.
The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.
After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.
After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.
“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.
Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.
The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.
However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.
The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
‘Valid option’ for partial breast irradiation in breast cancer
The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
- According to numerous guidelines, partial breast irradiation after lumpectomy is a sound approach for early-stage breast cancer, but there is a lack of consensus about treatment schedules.
- The investigators suggest that 30 Gy in five daily fractions is a “valid option” for these patients in a field that lacks consensus.
Study design
- The team reviewed 381 women with early breast cancer treated with this approach (30 Gy in five daily fractions) at their center from 2013 to 2022.
- Half of patients had left-sided tumors, 94.5% had invasive ductal carcinomas, 96.6% had grade 1 or grade 2 disease, and tumors were luminal like in 99.2% of patients.
- Following lumpectomy, women underwent partial breast irradiation to the tumor bed plus 15 mm of isometric expansion beyond it.
- Follow-up was a median of 28 months.
Key results
- Seven patients (2%) had a local recurrence, of which two were in the treatment field.
- Three-year local control, disease-free survival, and overall survival were high (97.5%, 95.7%, and 96.9%, respectively).
- Nearly 90% of patients and 97% of physicians reported good or excellent cosmesis.
- Ten patients (2.9%) had grade 2 late toxicities, including edema, asthenia, and fibrosis; there were no grade 3 or higher adverse events.
- Five patients (1.5%) had late cardiac major events, four of whom were treated on the right breast; three patients (0.9%) had late pulmonary fibrosis.
- The safety and efficacy outcomes are in line with previous reports, including those that used different dosage and/or fractionation schedules.
Limitations
- The study was retrospective, with a relatively short follow-up.
- Quality of life was not assessed.
- There was no objective baseline measure of cosmesis against which to compare cosmetic results.
Disclosures
- There was no funding for the study, and the investigators didn’t have any conflicts of interest to report.
This is a summary of a preprint research study, “One-Week External Beam Partial Breast Irradiation: Survival and Toxicity Outcomes,” led by Riccardo Ray Colciago from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. The study has not been peer reviewed. The full text can be found at researchsquare.com.
A version of this article first appeared on Medscape.com.
The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
- According to numerous guidelines, partial breast irradiation after lumpectomy is a sound approach for early-stage breast cancer, but there is a lack of consensus about treatment schedules.
- The investigators suggest that 30 Gy in five daily fractions is a “valid option” for these patients in a field that lacks consensus.
Study design
- The team reviewed 381 women with early breast cancer treated with this approach (30 Gy in five daily fractions) at their center from 2013 to 2022.
- Half of patients had left-sided tumors, 94.5% had invasive ductal carcinomas, 96.6% had grade 1 or grade 2 disease, and tumors were luminal like in 99.2% of patients.
- Following lumpectomy, women underwent partial breast irradiation to the tumor bed plus 15 mm of isometric expansion beyond it.
- Follow-up was a median of 28 months.
Key results
- Seven patients (2%) had a local recurrence, of which two were in the treatment field.
- Three-year local control, disease-free survival, and overall survival were high (97.5%, 95.7%, and 96.9%, respectively).
- Nearly 90% of patients and 97% of physicians reported good or excellent cosmesis.
- Ten patients (2.9%) had grade 2 late toxicities, including edema, asthenia, and fibrosis; there were no grade 3 or higher adverse events.
- Five patients (1.5%) had late cardiac major events, four of whom were treated on the right breast; three patients (0.9%) had late pulmonary fibrosis.
- The safety and efficacy outcomes are in line with previous reports, including those that used different dosage and/or fractionation schedules.
Limitations
- The study was retrospective, with a relatively short follow-up.
- Quality of life was not assessed.
- There was no objective baseline measure of cosmesis against which to compare cosmetic results.
Disclosures
- There was no funding for the study, and the investigators didn’t have any conflicts of interest to report.
This is a summary of a preprint research study, “One-Week External Beam Partial Breast Irradiation: Survival and Toxicity Outcomes,” led by Riccardo Ray Colciago from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. The study has not been peer reviewed. The full text can be found at researchsquare.com.
A version of this article first appeared on Medscape.com.
The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
- According to numerous guidelines, partial breast irradiation after lumpectomy is a sound approach for early-stage breast cancer, but there is a lack of consensus about treatment schedules.
- The investigators suggest that 30 Gy in five daily fractions is a “valid option” for these patients in a field that lacks consensus.
Study design
- The team reviewed 381 women with early breast cancer treated with this approach (30 Gy in five daily fractions) at their center from 2013 to 2022.
- Half of patients had left-sided tumors, 94.5% had invasive ductal carcinomas, 96.6% had grade 1 or grade 2 disease, and tumors were luminal like in 99.2% of patients.
- Following lumpectomy, women underwent partial breast irradiation to the tumor bed plus 15 mm of isometric expansion beyond it.
- Follow-up was a median of 28 months.
Key results
- Seven patients (2%) had a local recurrence, of which two were in the treatment field.
- Three-year local control, disease-free survival, and overall survival were high (97.5%, 95.7%, and 96.9%, respectively).
- Nearly 90% of patients and 97% of physicians reported good or excellent cosmesis.
- Ten patients (2.9%) had grade 2 late toxicities, including edema, asthenia, and fibrosis; there were no grade 3 or higher adverse events.
- Five patients (1.5%) had late cardiac major events, four of whom were treated on the right breast; three patients (0.9%) had late pulmonary fibrosis.
- The safety and efficacy outcomes are in line with previous reports, including those that used different dosage and/or fractionation schedules.
Limitations
- The study was retrospective, with a relatively short follow-up.
- Quality of life was not assessed.
- There was no objective baseline measure of cosmesis against which to compare cosmetic results.
Disclosures
- There was no funding for the study, and the investigators didn’t have any conflicts of interest to report.
This is a summary of a preprint research study, “One-Week External Beam Partial Breast Irradiation: Survival and Toxicity Outcomes,” led by Riccardo Ray Colciago from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. The study has not been peer reviewed. The full text can be found at researchsquare.com.
A version of this article first appeared on Medscape.com.
Facial lipoatrophy with semaglutide-related weight loss
Ozempic and Wegovy are two prescription drugs that have transformed the management of type 2 diabetes and obesity. Both are a form of semaglutide; the Food and Drug Administration approved Ozempic for treating type 2 diabetes in 2017, followed by Wegovy in 2021 for weight loss in adults with obesity or those who are overweight and have least one weight-related health condition, such as hypertension or hypercholesterolemia. Ozempic is not approved for weight loss, but it has been prescribed off label for that purpose.
An effective treatment, participants with overweight or obesity in one study experienced almost a mean 15% drop in body weight with subcutaneous semaglutide administered once a week versus about 2% with placebo after 68 weeks.
In 2022, high demand and global supply constraints gave rise to shortages of both medications. The FDA reported a Wegovy shortage in March 2022, followed by an Ozempic shortage in August. Social media attention and increased off-label prescribing, with some patients purporting to have had significant improvements with weight loss and their quality of life, including having their clothing fit better and being able to bend over and tie their shoes, increased attention on these medications to the point that off-label prescribing of both drugs for weight loss resulted in some patients with type 2 diabetes unable to receive their medication on time. In late January 2023, NBC reported that Ozempic prescriptions had “tripled from 2021 to 2022,” based on data from the prescription drug discount company SingleCare.
Semaglutide is designed to mimic a hormone that signals to the brain when a person is full and promotes the release of insulin. In turn, the medications can result in lower blood glucose levels, appetite suppression, and reduced caloric intake. Injected once weekly, the medication, a glucagonlike peptide–1 receptor agonist, specifically, activates GLP-1 receptors in the brain, increasing insulin secretion, decreasing glucagon secretion, and delaying gastric emptying (acting as an incretin mimetic).
‘Ozempic face’
Common adverse events with semaglutide can include nausea, vomiting, diarrhea, abdominal pain, constipation, and injection-site reactions. Rare, but more severe adverse events may include thyroid C-cell tumor (in animal studies), medullary thyroid cancer risk, hypersensitivity reaction, anaphylaxis, acute renal injury, chronic renal failure exacerbation, pancreatitis, and cholelithiasis.
A less severe but noticeable side effect that has gained attention is facial wasting and aging, reportedly coined “Ozempic face” by a dermatologist interviewed for an article published in January in The New York Times.
As of Feb. 9, TikTok videos from individuals describing their personal experiences, health care professionals, and others with the tag #ozempicface had 4.8 million views.
Theories as to why noticeable facial changes occur with these medications include: accelerated loss of facial pads that already tend to diminish or shift with normal aging, as well as the inability of skin elasticity to keep up with the loss of volume (fat), resulting in more prominent hanging skin and the appearance of “jowls.” Wan and colleagues have described the fat pad distribution in the face and the facial aging that occurs as a result of the loss and shifting of these fat pads over time.
In the same way that we use facial fillers to help treat and correct volume/fat loss associated with photoaging, facial fillers may be used to help restore volume where it’s been lost after weight loss. The sagging skin or loss of elasticity often associated with Ozempic-related weight loss or with rapid or noticeable weight loss in general, may or may not also require other interventions that include treatment with tissue tightening devices – such as radiofrequency energy, high-focused ultrasound energy, threads, and/or surgery – such as a face lift. The potential high cost of both off-label prescribing of these medications (especially without use of prescription health insurance) as well as treatment to correct any facial wasting has also received attention in news media and social media discussions of this topic.
Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at [email protected]. She has no relevant disclosures.
*Correction 1/28/23: An earlier version of this story misstated the approval date of Wegovy. It was in 2021.
Ozempic and Wegovy are two prescription drugs that have transformed the management of type 2 diabetes and obesity. Both are a form of semaglutide; the Food and Drug Administration approved Ozempic for treating type 2 diabetes in 2017, followed by Wegovy in 2021 for weight loss in adults with obesity or those who are overweight and have least one weight-related health condition, such as hypertension or hypercholesterolemia. Ozempic is not approved for weight loss, but it has been prescribed off label for that purpose.
An effective treatment, participants with overweight or obesity in one study experienced almost a mean 15% drop in body weight with subcutaneous semaglutide administered once a week versus about 2% with placebo after 68 weeks.
In 2022, high demand and global supply constraints gave rise to shortages of both medications. The FDA reported a Wegovy shortage in March 2022, followed by an Ozempic shortage in August. Social media attention and increased off-label prescribing, with some patients purporting to have had significant improvements with weight loss and their quality of life, including having their clothing fit better and being able to bend over and tie their shoes, increased attention on these medications to the point that off-label prescribing of both drugs for weight loss resulted in some patients with type 2 diabetes unable to receive their medication on time. In late January 2023, NBC reported that Ozempic prescriptions had “tripled from 2021 to 2022,” based on data from the prescription drug discount company SingleCare.
Semaglutide is designed to mimic a hormone that signals to the brain when a person is full and promotes the release of insulin. In turn, the medications can result in lower blood glucose levels, appetite suppression, and reduced caloric intake. Injected once weekly, the medication, a glucagonlike peptide–1 receptor agonist, specifically, activates GLP-1 receptors in the brain, increasing insulin secretion, decreasing glucagon secretion, and delaying gastric emptying (acting as an incretin mimetic).
‘Ozempic face’
Common adverse events with semaglutide can include nausea, vomiting, diarrhea, abdominal pain, constipation, and injection-site reactions. Rare, but more severe adverse events may include thyroid C-cell tumor (in animal studies), medullary thyroid cancer risk, hypersensitivity reaction, anaphylaxis, acute renal injury, chronic renal failure exacerbation, pancreatitis, and cholelithiasis.
A less severe but noticeable side effect that has gained attention is facial wasting and aging, reportedly coined “Ozempic face” by a dermatologist interviewed for an article published in January in The New York Times.
As of Feb. 9, TikTok videos from individuals describing their personal experiences, health care professionals, and others with the tag #ozempicface had 4.8 million views.
Theories as to why noticeable facial changes occur with these medications include: accelerated loss of facial pads that already tend to diminish or shift with normal aging, as well as the inability of skin elasticity to keep up with the loss of volume (fat), resulting in more prominent hanging skin and the appearance of “jowls.” Wan and colleagues have described the fat pad distribution in the face and the facial aging that occurs as a result of the loss and shifting of these fat pads over time.
In the same way that we use facial fillers to help treat and correct volume/fat loss associated with photoaging, facial fillers may be used to help restore volume where it’s been lost after weight loss. The sagging skin or loss of elasticity often associated with Ozempic-related weight loss or with rapid or noticeable weight loss in general, may or may not also require other interventions that include treatment with tissue tightening devices – such as radiofrequency energy, high-focused ultrasound energy, threads, and/or surgery – such as a face lift. The potential high cost of both off-label prescribing of these medications (especially without use of prescription health insurance) as well as treatment to correct any facial wasting has also received attention in news media and social media discussions of this topic.
Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at [email protected]. She has no relevant disclosures.
*Correction 1/28/23: An earlier version of this story misstated the approval date of Wegovy. It was in 2021.
Ozempic and Wegovy are two prescription drugs that have transformed the management of type 2 diabetes and obesity. Both are a form of semaglutide; the Food and Drug Administration approved Ozempic for treating type 2 diabetes in 2017, followed by Wegovy in 2021 for weight loss in adults with obesity or those who are overweight and have least one weight-related health condition, such as hypertension or hypercholesterolemia. Ozempic is not approved for weight loss, but it has been prescribed off label for that purpose.
An effective treatment, participants with overweight or obesity in one study experienced almost a mean 15% drop in body weight with subcutaneous semaglutide administered once a week versus about 2% with placebo after 68 weeks.
In 2022, high demand and global supply constraints gave rise to shortages of both medications. The FDA reported a Wegovy shortage in March 2022, followed by an Ozempic shortage in August. Social media attention and increased off-label prescribing, with some patients purporting to have had significant improvements with weight loss and their quality of life, including having their clothing fit better and being able to bend over and tie their shoes, increased attention on these medications to the point that off-label prescribing of both drugs for weight loss resulted in some patients with type 2 diabetes unable to receive their medication on time. In late January 2023, NBC reported that Ozempic prescriptions had “tripled from 2021 to 2022,” based on data from the prescription drug discount company SingleCare.
Semaglutide is designed to mimic a hormone that signals to the brain when a person is full and promotes the release of insulin. In turn, the medications can result in lower blood glucose levels, appetite suppression, and reduced caloric intake. Injected once weekly, the medication, a glucagonlike peptide–1 receptor agonist, specifically, activates GLP-1 receptors in the brain, increasing insulin secretion, decreasing glucagon secretion, and delaying gastric emptying (acting as an incretin mimetic).
‘Ozempic face’
Common adverse events with semaglutide can include nausea, vomiting, diarrhea, abdominal pain, constipation, and injection-site reactions. Rare, but more severe adverse events may include thyroid C-cell tumor (in animal studies), medullary thyroid cancer risk, hypersensitivity reaction, anaphylaxis, acute renal injury, chronic renal failure exacerbation, pancreatitis, and cholelithiasis.
A less severe but noticeable side effect that has gained attention is facial wasting and aging, reportedly coined “Ozempic face” by a dermatologist interviewed for an article published in January in The New York Times.
As of Feb. 9, TikTok videos from individuals describing their personal experiences, health care professionals, and others with the tag #ozempicface had 4.8 million views.
Theories as to why noticeable facial changes occur with these medications include: accelerated loss of facial pads that already tend to diminish or shift with normal aging, as well as the inability of skin elasticity to keep up with the loss of volume (fat), resulting in more prominent hanging skin and the appearance of “jowls.” Wan and colleagues have described the fat pad distribution in the face and the facial aging that occurs as a result of the loss and shifting of these fat pads over time.
In the same way that we use facial fillers to help treat and correct volume/fat loss associated with photoaging, facial fillers may be used to help restore volume where it’s been lost after weight loss. The sagging skin or loss of elasticity often associated with Ozempic-related weight loss or with rapid or noticeable weight loss in general, may or may not also require other interventions that include treatment with tissue tightening devices – such as radiofrequency energy, high-focused ultrasound energy, threads, and/or surgery – such as a face lift. The potential high cost of both off-label prescribing of these medications (especially without use of prescription health insurance) as well as treatment to correct any facial wasting has also received attention in news media and social media discussions of this topic.
Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at [email protected]. She has no relevant disclosures.
*Correction 1/28/23: An earlier version of this story misstated the approval date of Wegovy. It was in 2021.
Novel neuroprotective agent promising in stroke
preliminary results of a first-in-human study show.
The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.
Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.
The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Best doses
The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.
The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.
The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.
“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.
Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.
Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.
“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.
Those who were eligible also received tissue plasminogen activator.
The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
Lower mortality
At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).
The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”
The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).
About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.
A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).
This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
Clear shift in disability
“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.
He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.
“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”
These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”
Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.
Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”
The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”
The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
‘Very robust results’
In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”
“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.
He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.
“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”
However, he stressed the drug “is not ready for prime-time practice.”
“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.
The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
preliminary results of a first-in-human study show.
The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.
Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.
The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Best doses
The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.
The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.
The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.
“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.
Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.
Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.
“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.
Those who were eligible also received tissue plasminogen activator.
The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
Lower mortality
At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).
The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”
The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).
About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.
A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).
This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
Clear shift in disability
“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.
He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.
“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”
These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”
Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.
Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”
The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”
The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
‘Very robust results’
In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”
“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.
He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.
“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”
However, he stressed the drug “is not ready for prime-time practice.”
“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.
The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
preliminary results of a first-in-human study show.
The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.
Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.
The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Best doses
The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.
The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.
The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.
“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.
Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.
Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.
“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.
Those who were eligible also received tissue plasminogen activator.
The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
Lower mortality
At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).
The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”
The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).
About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.
A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).
This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
Clear shift in disability
“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.
He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.
“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”
These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”
Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.
Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”
The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”
The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
‘Very robust results’
In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”
“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.
He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.
“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”
However, he stressed the drug “is not ready for prime-time practice.”
“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.
The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2023