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Combine calculators and medications to manage risk in osteoporosis patients
Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.
Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.
Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).
When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.
During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”
Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.
In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.
As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.
When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.
Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.
Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.
“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.
However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.
One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.
Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.
Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.
Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.
Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.
Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).
When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.
During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”
Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.
In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.
As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.
When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.
Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.
Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.
“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.
However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.
One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.
Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.
Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.
Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.
Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.
Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).
When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.
During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”
Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.
In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.
As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.
When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.
Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.
Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.
“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.
However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.
One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.
Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.
Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.
FROM MEDS 2020
CAR T for all R/R DLBCL patients: The jury is still out
Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.
CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.
In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.
Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.
The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.
The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).
These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”
“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.
“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.
The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.
“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”
CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.
However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”
Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.
CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.
In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.
Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.
The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.
The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).
These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”
“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.
“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.
The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.
“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”
CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.
However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”
Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.
CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.
In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.
Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.
The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.
The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).
These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”
“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.
“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.
The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.
“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”
CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.
However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”
Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
FROM NCCN HEMATOLOGIC MALIGNANCIES
Brain imaging reveals a neural basis for partisan politics
The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.
Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.
“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.
“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.
The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
Hardwired to disagree?
The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.
They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.
These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.
After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.
The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.
Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.
Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.
For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.
“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.
“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.
Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.
“ – for example, by framing messages to appeal to the core values of the respective voter,” he said.
Brain stimulation to alter political perception?
Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”
The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”
“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.
The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.
Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.
“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.
“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.
The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
Hardwired to disagree?
The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.
They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.
These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.
After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.
The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.
Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.
Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.
For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.
“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.
“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.
Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.
“ – for example, by framing messages to appeal to the core values of the respective voter,” he said.
Brain stimulation to alter political perception?
Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”
The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”
“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.
The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.
Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.
“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.
“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.
The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
Hardwired to disagree?
The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.
They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.
These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.
After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.
The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.
Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.
Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.
For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.
“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.
“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.
Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.
“ – for example, by framing messages to appeal to the core values of the respective voter,” he said.
Brain stimulation to alter political perception?
Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”
The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”
“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.
The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The new one-percenters: Children with COVID-19
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.
There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.
The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.
Other measures largely put small states at the extremes:
- North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
- Vermont has the lowest cumulative rate: 190.5 per 100,000.
- Wyoming has the highest proportion of cases in children: 27.7%.
- New Jersey has the lowest proportion of child cases: 4.6%.
There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.
There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.
The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.
Other measures largely put small states at the extremes:
- North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
- Vermont has the lowest cumulative rate: 190.5 per 100,000.
- Wyoming has the highest proportion of cases in children: 27.7%.
- New Jersey has the lowest proportion of child cases: 4.6%.
There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.
There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.
The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.
Other measures largely put small states at the extremes:
- North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
- Vermont has the lowest cumulative rate: 190.5 per 100,000.
- Wyoming has the highest proportion of cases in children: 27.7%.
- New Jersey has the lowest proportion of child cases: 4.6%.
There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.
COVID-19: Immunity from antibodies may decline rapidly
Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.
An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.
The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.
Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.
“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”
Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
Antibody prevalence declined in all adults
Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.
There were 17,576 positive tests over the three rounds.
Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.
The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.
No change was seen in positive antibody tests in health care workers over the 3 months.
The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.
Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
Results ‘weaken argument for herd immunity’
Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”
However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.
Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.
However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.
“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.
Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
This article first appeared on Medscape.com.
Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.
An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.
The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.
Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.
“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”
Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
Antibody prevalence declined in all adults
Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.
There were 17,576 positive tests over the three rounds.
Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.
The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.
No change was seen in positive antibody tests in health care workers over the 3 months.
The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.
Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
Results ‘weaken argument for herd immunity’
Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”
However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.
Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.
However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.
“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.
Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
This article first appeared on Medscape.com.
Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.
An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.
The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.
Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.
“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”
Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
Antibody prevalence declined in all adults
Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.
There were 17,576 positive tests over the three rounds.
Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.
The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.
No change was seen in positive antibody tests in health care workers over the 3 months.
The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.
Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
Results ‘weaken argument for herd immunity’
Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”
However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.
Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.
However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.
“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.
Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
This article first appeared on Medscape.com.
Ataluren delays disease milestones in patients with nonsense mutation DMD
(nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.
DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
Comparing treatment and standard of care
Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.
Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.
Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
Treatment delayed disease milestones
Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.
The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.
SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.
(nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.
DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
Comparing treatment and standard of care
Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.
Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.
Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
Treatment delayed disease milestones
Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.
The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.
SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.
(nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.
DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
Comparing treatment and standard of care
Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.
Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.
Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
Treatment delayed disease milestones
Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.
The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.
SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.
FROM CNS-ICNA 2020
Newer DMTs are more effective than injectable DMTs in pediatric MS
Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
An examination of medical records
MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.
Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.
The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
Most patients initiated injectable DMTs
Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.
The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.
In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.
The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.
SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.
Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
An examination of medical records
MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.
Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.
The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
Most patients initiated injectable DMTs
Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.
The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.
In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.
The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.
SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.
Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
An examination of medical records
MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.
Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.
The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
Most patients initiated injectable DMTs
Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.
The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.
In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.
The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.
SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.
FROM CNS-ICNA 2020
Study supports halting antiseizure medications after neonatal seizures
Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.
“,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.
“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.”
The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.
The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.
“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.
After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.
The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.
“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”
The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.
SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.
Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.
“,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.
“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.”
The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.
The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.
“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.
After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.
The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.
“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”
The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.
SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.
Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.
“,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.
“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.”
The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.
The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.
“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.
After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.
The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.
“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”
The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.
SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.
FROM CNS-ICNA 2020
Valvular disease and COVID-19 are a deadly mix; don’t delay intervention
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
FROM TCT 2020
PPI use associated with all-cause and cause-specific mortality
Background: PPI use has previously been associated with an increased risk of acute kidney injury, Clostridium difficile infection, osteoporosis, dementia, and all-cause mortality. An estimation of the level of mortality risk, as well as cause-specific mortality risk, may better inform decisions about prescribing PPIs.
Study design: Longitudinal observational cohort.
Setting: Department of Veterans Affairs.
Synopsis: Using a cohort of veterans newly prescribed acid suppression therapy in 2002-2004, 157,625 new PPI users were compared with 56,842 new H2 receptor–blocker users. Over the following 10 years, a specific cause of death was determined using national death index data. In that period, 37.3% of patients died, with PPI use associated with 45.2 excess deaths per 1,000 patients (95% confidence interval, 28.2-61.4). There were significant associations with the following specific causes of death: circulatory system diseases (17.5 excess deaths per 1,000 patients, 95% CI, 5.5-28.8), neoplasms (12.9; 95% CI, 1.2-24.3), genitourinary system diseases including chronic kidney disease (6.3; 95% CI, 1.6-7.0), and infectious/parasitic diseases (4.2; 95% CI, 3.2-9.2).
Limitations include the observational study design and potential for confounding variables not accounted for by the researchers. There is also a question of broader applicability given the VA patient population. Nevertheless, this study adds to growing evidence regarding risks associated with PPI use. Clinicians should consider prescribing PPIs only for indications and durations where it is known to offer benefit in order minimize risk of adverse events.
Bottom line: PPI use is associated with an excess risk of death, particularly death caused by cardiovascular disease, malignancy, genitourinary diseases, and infection.
CITATION: Xie Y et al. Estimates of all-cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: Cohort study. BMJ. 2019 May 29;365:l1580.
Dr. Kruse is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.
Background: PPI use has previously been associated with an increased risk of acute kidney injury, Clostridium difficile infection, osteoporosis, dementia, and all-cause mortality. An estimation of the level of mortality risk, as well as cause-specific mortality risk, may better inform decisions about prescribing PPIs.
Study design: Longitudinal observational cohort.
Setting: Department of Veterans Affairs.
Synopsis: Using a cohort of veterans newly prescribed acid suppression therapy in 2002-2004, 157,625 new PPI users were compared with 56,842 new H2 receptor–blocker users. Over the following 10 years, a specific cause of death was determined using national death index data. In that period, 37.3% of patients died, with PPI use associated with 45.2 excess deaths per 1,000 patients (95% confidence interval, 28.2-61.4). There were significant associations with the following specific causes of death: circulatory system diseases (17.5 excess deaths per 1,000 patients, 95% CI, 5.5-28.8), neoplasms (12.9; 95% CI, 1.2-24.3), genitourinary system diseases including chronic kidney disease (6.3; 95% CI, 1.6-7.0), and infectious/parasitic diseases (4.2; 95% CI, 3.2-9.2).
Limitations include the observational study design and potential for confounding variables not accounted for by the researchers. There is also a question of broader applicability given the VA patient population. Nevertheless, this study adds to growing evidence regarding risks associated with PPI use. Clinicians should consider prescribing PPIs only for indications and durations where it is known to offer benefit in order minimize risk of adverse events.
Bottom line: PPI use is associated with an excess risk of death, particularly death caused by cardiovascular disease, malignancy, genitourinary diseases, and infection.
CITATION: Xie Y et al. Estimates of all-cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: Cohort study. BMJ. 2019 May 29;365:l1580.
Dr. Kruse is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.
Background: PPI use has previously been associated with an increased risk of acute kidney injury, Clostridium difficile infection, osteoporosis, dementia, and all-cause mortality. An estimation of the level of mortality risk, as well as cause-specific mortality risk, may better inform decisions about prescribing PPIs.
Study design: Longitudinal observational cohort.
Setting: Department of Veterans Affairs.
Synopsis: Using a cohort of veterans newly prescribed acid suppression therapy in 2002-2004, 157,625 new PPI users were compared with 56,842 new H2 receptor–blocker users. Over the following 10 years, a specific cause of death was determined using national death index data. In that period, 37.3% of patients died, with PPI use associated with 45.2 excess deaths per 1,000 patients (95% confidence interval, 28.2-61.4). There were significant associations with the following specific causes of death: circulatory system diseases (17.5 excess deaths per 1,000 patients, 95% CI, 5.5-28.8), neoplasms (12.9; 95% CI, 1.2-24.3), genitourinary system diseases including chronic kidney disease (6.3; 95% CI, 1.6-7.0), and infectious/parasitic diseases (4.2; 95% CI, 3.2-9.2).
Limitations include the observational study design and potential for confounding variables not accounted for by the researchers. There is also a question of broader applicability given the VA patient population. Nevertheless, this study adds to growing evidence regarding risks associated with PPI use. Clinicians should consider prescribing PPIs only for indications and durations where it is known to offer benefit in order minimize risk of adverse events.
Bottom line: PPI use is associated with an excess risk of death, particularly death caused by cardiovascular disease, malignancy, genitourinary diseases, and infection.
CITATION: Xie Y et al. Estimates of all-cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: Cohort study. BMJ. 2019 May 29;365:l1580.
Dr. Kruse is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.