Neurology Reviews

SAN DIEGO — Nearly one in three patients with migraine are reluctant to seek medical help and many blame healthcare providers, results of a recent survey showed.

Participants cited concerns that their complaints would be dismissed, a belief that healthcare providers could offer no additional help, and a prior unsuccessful clinician visit as reasons for not seeking care. Survey respondents saw an average of four clinicians before finally receiving a diagnosis.

“I was shocked that a third of patients were reluctant to seek care,” said study investigator Elizabeth K. Seng, PhD, associate professor, Ferkauf Graduate School of Psychology, Yeshiva University, and research associate professor, department of neurology, Albert Einstein College of Medicine, both in New York City. “That just shows a much higher level of medical distress than I expected from this community of people who are obviously suffering from this significant neurologic disease.”

The findings were presented at the annual meeting of the American Headache Society.
 

‘Significant Disease’

The study included 500 adults with migraine (mean age, 40 years) who signed up for a patient support group sponsored by Eli Lilly and completed a comprehensive survey. Respondents were mostly female, White, non-Hispanic, and well-educated individuals.

Half of participants had episodic migraines, and half had chronic migraines; 46% reported experiencing anxiety and 33% reported depression.

Almost all respondents had initiated treatment with a first calcitonin gene-related peptide (CGRP) monoclonal antibody.

“These are people who have significant enough disease that eventually they needed our top-tier preventive medication,” Dr. Seng said.

Participants answered a variety of questions pertaining to disease factors and treatment seeking. Just over 70% said they suspected they had migraine prior to diagnosis, “which means for almost 30%, it was a surprise when they received the diagnosis,” said Dr. Seng. 

Nearly 40% reported that a relative first suggested they may have migraine, and 33% suspected it themselves. Only 17.4% said a healthcare provider suggested they may have the condition.

Almost a third of respondents (30.5%) reported they were reluctant to seek medical help.

“Some said they didn’t think their physician could do anything more than they were already doing for themselves, or that they’d be taken seriously, or they had had talked to doctors before and this wasn’t helpful,” said Dr. Seng. 

These responses speak to the need for better public health messaging, she said. “People have this idea that migraine attacks aren’t a big deal when, in fact, these attacks area big deal and certainly deserve treatment.” 

Family and friends were participants’ most common source of information on migraine, followed by the Internet. “This highlights the importance of getting migraine-related information out there so that when people talk to their friends and family, they’re receiving accurate information,” said Dr. Seng.

When asked about the path to a diagnosis, respondents reported consulting an average of four providers before receiving an accurate diagnosis. “That’s pretty remarkable,” Dr. Seng said.

An increase in frequency or severity of migraine attacks or attacks that interfered with work or school “pushed people over the threshold to seek care,” Dr. Seng said. 

A subset of patients was asked about the factors they believed could help with migraine attacks. Of these, 80% cited diet and 70% stress reduction. Supplements, exercise, and relaxation techniques were cited much less frequently, said Dr. Seng. 

The mean age of respondents’ migraine diagnosis was 26 years, so there was about 18 years from the time of diagnosis to participation in the survey, which could introduce recall bias. Other potential limitations included the fact that the survey had no open-ended questions, and men and ethnic minorities were underrepresented. 
 

Useful Data

Commenting on the study findings, Nina Riggins, MD, PhD, president, Brain Performance Center and Research Institute, and director of the Headache Center at The Neuron Clinic, San Diego, California, said the survey findings are “very useful” and highlight “significant opportunities for improvement in migraine education for clinicians and people living with migraine disease.”

The fact that participants reported consulting an average of four healthcare providers before receiving an accurate diagnosis underscores the importance of providing clinicians with tools to identify migraine, she said.

This is especially relevant as new migraine therapies that may improve efficacy and have fewer side effects become available, she added. 

“It would be interesting to see in future studies if migraine recognition by non-headache specialists improved after CGRP-blocking medications for migraine management became available,” said Dr. Riggins, who is cochair of the AHS First Contact program which is aimed at improving headache management in primary care.

She added that she and her colleagues will keep these survey results in mind when creating future educational materials for clinicians.

The study was supported by Eli Lily. Dr. Seng is a consultant for GlaxoSmithKline, Theranica, and Abbvie, and receives research support from the National Institutes of Health, National Center for Complementary and Integrative Health, National Institute of Neurological Disorders and Stroke, Veterans Health Administration, Cystic Fibrosis Foundation, and the American Heart Association. Dr. Riggins reported no relevant conflicts.

A version of this article appeared on Medscape.com.

SAN DIEGO — Nearly one in three patients with migraine are reluctant to seek medical help and many blame healthcare providers, results of a recent survey showed.

Participants cited concerns that their complaints would be dismissed, a belief that healthcare providers could offer no additional help, and a prior unsuccessful clinician visit as reasons for not seeking care. Survey respondents saw an average of four clinicians before finally receiving a diagnosis.

“I was shocked that a third of patients were reluctant to seek care,” said study investigator Elizabeth K. Seng, PhD, associate professor, Ferkauf Graduate School of Psychology, Yeshiva University, and research associate professor, department of neurology, Albert Einstein College of Medicine, both in New York City. “That just shows a much higher level of medical distress than I expected from this community of people who are obviously suffering from this significant neurologic disease.”

The findings were presented at the annual meeting of the American Headache Society.
 

‘Significant Disease’

The study included 500 adults with migraine (mean age, 40 years) who signed up for a patient support group sponsored by Eli Lilly and completed a comprehensive survey. Respondents were mostly female, White, non-Hispanic, and well-educated individuals.

Half of participants had episodic migraines, and half had chronic migraines; 46% reported experiencing anxiety and 33% reported depression.

Almost all respondents had initiated treatment with a first calcitonin gene-related peptide (CGRP) monoclonal antibody.

“These are people who have significant enough disease that eventually they needed our top-tier preventive medication,” Dr. Seng said.

Participants answered a variety of questions pertaining to disease factors and treatment seeking. Just over 70% said they suspected they had migraine prior to diagnosis, “which means for almost 30%, it was a surprise when they received the diagnosis,” said Dr. Seng. 

Nearly 40% reported that a relative first suggested they may have migraine, and 33% suspected it themselves. Only 17.4% said a healthcare provider suggested they may have the condition.

Almost a third of respondents (30.5%) reported they were reluctant to seek medical help.

“Some said they didn’t think their physician could do anything more than they were already doing for themselves, or that they’d be taken seriously, or they had had talked to doctors before and this wasn’t helpful,” said Dr. Seng. 

These responses speak to the need for better public health messaging, she said. “People have this idea that migraine attacks aren’t a big deal when, in fact, these attacks area big deal and certainly deserve treatment.” 

Family and friends were participants’ most common source of information on migraine, followed by the Internet. “This highlights the importance of getting migraine-related information out there so that when people talk to their friends and family, they’re receiving accurate information,” said Dr. Seng.

When asked about the path to a diagnosis, respondents reported consulting an average of four providers before receiving an accurate diagnosis. “That’s pretty remarkable,” Dr. Seng said.

An increase in frequency or severity of migraine attacks or attacks that interfered with work or school “pushed people over the threshold to seek care,” Dr. Seng said. 

A subset of patients was asked about the factors they believed could help with migraine attacks. Of these, 80% cited diet and 70% stress reduction. Supplements, exercise, and relaxation techniques were cited much less frequently, said Dr. Seng. 

The mean age of respondents’ migraine diagnosis was 26 years, so there was about 18 years from the time of diagnosis to participation in the survey, which could introduce recall bias. Other potential limitations included the fact that the survey had no open-ended questions, and men and ethnic minorities were underrepresented. 
 

Useful Data

Commenting on the study findings, Nina Riggins, MD, PhD, president, Brain Performance Center and Research Institute, and director of the Headache Center at The Neuron Clinic, San Diego, California, said the survey findings are “very useful” and highlight “significant opportunities for improvement in migraine education for clinicians and people living with migraine disease.”

The fact that participants reported consulting an average of four healthcare providers before receiving an accurate diagnosis underscores the importance of providing clinicians with tools to identify migraine, she said.

This is especially relevant as new migraine therapies that may improve efficacy and have fewer side effects become available, she added. 

“It would be interesting to see in future studies if migraine recognition by non-headache specialists improved after CGRP-blocking medications for migraine management became available,” said Dr. Riggins, who is cochair of the AHS First Contact program which is aimed at improving headache management in primary care.

She added that she and her colleagues will keep these survey results in mind when creating future educational materials for clinicians.

The study was supported by Eli Lily. Dr. Seng is a consultant for GlaxoSmithKline, Theranica, and Abbvie, and receives research support from the National Institutes of Health, National Center for Complementary and Integrative Health, National Institute of Neurological Disorders and Stroke, Veterans Health Administration, Cystic Fibrosis Foundation, and the American Heart Association. Dr. Riggins reported no relevant conflicts.

A version of this article appeared on Medscape.com.

SAN DIEGO — Nearly one in three patients with migraine are reluctant to seek medical help and many blame healthcare providers, results of a recent survey showed.

Participants cited concerns that their complaints would be dismissed, a belief that healthcare providers could offer no additional help, and a prior unsuccessful clinician visit as reasons for not seeking care. Survey respondents saw an average of four clinicians before finally receiving a diagnosis.

“I was shocked that a third of patients were reluctant to seek care,” said study investigator Elizabeth K. Seng, PhD, associate professor, Ferkauf Graduate School of Psychology, Yeshiva University, and research associate professor, department of neurology, Albert Einstein College of Medicine, both in New York City. “That just shows a much higher level of medical distress than I expected from this community of people who are obviously suffering from this significant neurologic disease.”

The findings were presented at the annual meeting of the American Headache Society.
 

‘Significant Disease’

The study included 500 adults with migraine (mean age, 40 years) who signed up for a patient support group sponsored by Eli Lilly and completed a comprehensive survey. Respondents were mostly female, White, non-Hispanic, and well-educated individuals.

Half of participants had episodic migraines, and half had chronic migraines; 46% reported experiencing anxiety and 33% reported depression.

Almost all respondents had initiated treatment with a first calcitonin gene-related peptide (CGRP) monoclonal antibody.

“These are people who have significant enough disease that eventually they needed our top-tier preventive medication,” Dr. Seng said.

Participants answered a variety of questions pertaining to disease factors and treatment seeking. Just over 70% said they suspected they had migraine prior to diagnosis, “which means for almost 30%, it was a surprise when they received the diagnosis,” said Dr. Seng. 

Nearly 40% reported that a relative first suggested they may have migraine, and 33% suspected it themselves. Only 17.4% said a healthcare provider suggested they may have the condition.

Almost a third of respondents (30.5%) reported they were reluctant to seek medical help.

“Some said they didn’t think their physician could do anything more than they were already doing for themselves, or that they’d be taken seriously, or they had had talked to doctors before and this wasn’t helpful,” said Dr. Seng. 

These responses speak to the need for better public health messaging, she said. “People have this idea that migraine attacks aren’t a big deal when, in fact, these attacks area big deal and certainly deserve treatment.” 

Family and friends were participants’ most common source of information on migraine, followed by the Internet. “This highlights the importance of getting migraine-related information out there so that when people talk to their friends and family, they’re receiving accurate information,” said Dr. Seng.

When asked about the path to a diagnosis, respondents reported consulting an average of four providers before receiving an accurate diagnosis. “That’s pretty remarkable,” Dr. Seng said.

An increase in frequency or severity of migraine attacks or attacks that interfered with work or school “pushed people over the threshold to seek care,” Dr. Seng said. 

A subset of patients was asked about the factors they believed could help with migraine attacks. Of these, 80% cited diet and 70% stress reduction. Supplements, exercise, and relaxation techniques were cited much less frequently, said Dr. Seng. 

The mean age of respondents’ migraine diagnosis was 26 years, so there was about 18 years from the time of diagnosis to participation in the survey, which could introduce recall bias. Other potential limitations included the fact that the survey had no open-ended questions, and men and ethnic minorities were underrepresented. 
 

Useful Data

Commenting on the study findings, Nina Riggins, MD, PhD, president, Brain Performance Center and Research Institute, and director of the Headache Center at The Neuron Clinic, San Diego, California, said the survey findings are “very useful” and highlight “significant opportunities for improvement in migraine education for clinicians and people living with migraine disease.”

The fact that participants reported consulting an average of four healthcare providers before receiving an accurate diagnosis underscores the importance of providing clinicians with tools to identify migraine, she said.

This is especially relevant as new migraine therapies that may improve efficacy and have fewer side effects become available, she added. 

“It would be interesting to see in future studies if migraine recognition by non-headache specialists improved after CGRP-blocking medications for migraine management became available,” said Dr. Riggins, who is cochair of the AHS First Contact program which is aimed at improving headache management in primary care.

She added that she and her colleagues will keep these survey results in mind when creating future educational materials for clinicians.

The study was supported by Eli Lily. Dr. Seng is a consultant for GlaxoSmithKline, Theranica, and Abbvie, and receives research support from the National Institutes of Health, National Center for Complementary and Integrative Health, National Institute of Neurological Disorders and Stroke, Veterans Health Administration, Cystic Fibrosis Foundation, and the American Heart Association. Dr. Riggins reported no relevant conflicts.

A version of this article appeared on Medscape.com.

An intensive lifestyle intervention significantly improved cognition and function in many patients with mild cognitive impairment (MCI) or early dementia due to Alzheimer’s disease, in what authors said is the first randomized controlled trial of intensive lifestyle modification for patients diagnosed with Alzheimer’s disease. Results could help physicians address patients at risk of Alzheimer’s disease who reject relevant testing because they believe nothing can forestall development of the disease, the authors added. The study was published online in Alzheimer’s Research & Therapy.

Although technology allows probable Alzheimer’s disease diagnosis years before clinical symptoms appear, wrote investigators led by Dean Ornish, MD, of the Preventive Medicine Research Institute in Sausalito, California, “many people do not want to know if they are likely to get Alzheimer’s disease if they do not believe they can do anything about it. If intensive lifestyle changes may cause improvement in cognition and function in MCI or early dementia due to Alzheimer’s disease, then it is reasonable to think that these lifestyle changes may also help to prevent MCI or early dementia due to Alzheimer’s disease.” As with cardiovascular disease, the authors added, preventing Alzheimer’s disease might require less intensive lifestyle modifications than treating it.
 

Study Methodology

Investigators randomized 26 patients with Montréal Cognitive Assessment scores of 18 or higher to an intensive intervention involving nutrition, exercise, and stress management techniques. To improve adherence, the protocol included participants’ spouses or caregivers.

Two patients, both in the treatment group, withdrew over logistical concerns.

After 20 weeks, treated patients exhibited statistically significant differences in several key measures versus a 25-patient usual-care control group. Scores that improved in the intervention group and worsened among controls included the following:

• Clinical Global Impression of Change (CGIC, P = .001)
• Clinical Dementia Rating-Global (CDR-Global, -0.04, P = .037)
• Clinical Dementia Rating Sum of Boxes (CDR-SB, +0.08, P = .032)
• Alzheimer’s Disease Assessment Scale (ADAS-Cog, -1.01, P = .053)

The validity of these changes in cognition and function, and possible biological mechanisms of improvement, were supported by statistically significant improvements in several clinically relevant biomarkers versus controls, the investigators wrote. These biomarkers included Abeta42/40 ratio, HbA1c, insulin, and glycoprotein acetylation. “This information may also help in predicting which patients are more likely to show improvements in cognition and function by making these intensive lifestyle changes,” the authors added.

In primary analysis, the degree of lifestyle changes required to stop progression of MCI ranged from 71.4% (ADAS-Cog) to 120.6% (CDR-SB). “This helps to explain why other studies of less intensive lifestyle interventions may not have been sufficient to stop deterioration or improve cognition and function,” the authors wrote. Moreover, they added, variable adherence might explain why in the intervention group, 10 patients improved their CGIC scores, while the rest held static or worsened.
 

Caveats

Alzheimer’s Association Vice President of Medical and Scientific Relations Heather M. Snyder, PhD, said, “This is an interesting paper in an important area of research and adds to the growing body of literature on how behavior or lifestyle may be related to cognitive decline. However, because this is a small phase 2 study, it is important for this or similar work to be done in larger, more diverse populations and over a longer duration of the intervention.” She was not involved with the study but was asked to comment.

Investigators chose the 20-week duration, they explained, because control-group patients likely would not refrain from trying the lifestyle intervention beyond that timeframe. Perhaps more importantly, challenges created by the COVID-19 pandemic required researchers to cut planned enrollment in half, eliminate planned MRI and amyloid PET scans, and reduce the number of cognition and function tests.

Such shortcomings limit what neurologists can glean and generalize from the study, said Dr. Snyder. “That said,” she added, “it does demonstrate the potential of an intensive behavior/lifestyle intervention, and the importance of this sort of research in Alzheimer’s and dementia.” Although the complexity of the interventions makes these studies challenging, she added, “it is important that we continue to advance larger, longer studies in more representative study populations to develop specific recommendations.”
 

Further Study

The Alzheimer’s Association’s U.S. POINTER study is the first large-scale study in the United States to explore the impact of comprehensive lifestyle changes on cognitive health. About 2000 older adults at risk for cognitive decline are participating, from diverse locations across the country. More than 25% of participants come from groups typically underrepresented in dementia research, said Dr. Snyder. Initial results are expected in summer 2025.

Future research also should explore reasons (beyond adherence) why some patients respond to lifestyle interventions better than others, and the potential synergy of lifestyle changes with drug therapies, wrote Dr. Ornish and colleagues.

“For now,” said Dr. Snyder, “there is an opportunity for providers to incorporate or expand messaging with their patients and families about the habits that they can incorporate into their daily lives. The Alzheimer’s Association offers 10 Healthy Habits for Your Brain — everyday actions that can make a difference for your brain health.”

Investigators received study funding from more than two dozen charitable foundations and other organizations. Dr. Snyder is a full-time employee of the Alzheimer’s Association and in this role, serves on the leadership team of the U.S. POINTER study. Her partner works for Abbott in an unrelated field. 

An intensive lifestyle intervention significantly improved cognition and function in many patients with mild cognitive impairment (MCI) or early dementia due to Alzheimer’s disease, in what authors said is the first randomized controlled trial of intensive lifestyle modification for patients diagnosed with Alzheimer’s disease. Results could help physicians address patients at risk of Alzheimer’s disease who reject relevant testing because they believe nothing can forestall development of the disease, the authors added. The study was published online in Alzheimer’s Research & Therapy.

Although technology allows probable Alzheimer’s disease diagnosis years before clinical symptoms appear, wrote investigators led by Dean Ornish, MD, of the Preventive Medicine Research Institute in Sausalito, California, “many people do not want to know if they are likely to get Alzheimer’s disease if they do not believe they can do anything about it. If intensive lifestyle changes may cause improvement in cognition and function in MCI or early dementia due to Alzheimer’s disease, then it is reasonable to think that these lifestyle changes may also help to prevent MCI or early dementia due to Alzheimer’s disease.” As with cardiovascular disease, the authors added, preventing Alzheimer’s disease might require less intensive lifestyle modifications than treating it.
 

Study Methodology

Investigators randomized 26 patients with Montréal Cognitive Assessment scores of 18 or higher to an intensive intervention involving nutrition, exercise, and stress management techniques. To improve adherence, the protocol included participants’ spouses or caregivers.

Two patients, both in the treatment group, withdrew over logistical concerns.

After 20 weeks, treated patients exhibited statistically significant differences in several key measures versus a 25-patient usual-care control group. Scores that improved in the intervention group and worsened among controls included the following:

• Clinical Global Impression of Change (CGIC, P = .001)
• Clinical Dementia Rating-Global (CDR-Global, -0.04, P = .037)
• Clinical Dementia Rating Sum of Boxes (CDR-SB, +0.08, P = .032)
• Alzheimer’s Disease Assessment Scale (ADAS-Cog, -1.01, P = .053)

The validity of these changes in cognition and function, and possible biological mechanisms of improvement, were supported by statistically significant improvements in several clinically relevant biomarkers versus controls, the investigators wrote. These biomarkers included Abeta42/40 ratio, HbA1c, insulin, and glycoprotein acetylation. “This information may also help in predicting which patients are more likely to show improvements in cognition and function by making these intensive lifestyle changes,” the authors added.

In primary analysis, the degree of lifestyle changes required to stop progression of MCI ranged from 71.4% (ADAS-Cog) to 120.6% (CDR-SB). “This helps to explain why other studies of less intensive lifestyle interventions may not have been sufficient to stop deterioration or improve cognition and function,” the authors wrote. Moreover, they added, variable adherence might explain why in the intervention group, 10 patients improved their CGIC scores, while the rest held static or worsened.
 

Caveats

Alzheimer’s Association Vice President of Medical and Scientific Relations Heather M. Snyder, PhD, said, “This is an interesting paper in an important area of research and adds to the growing body of literature on how behavior or lifestyle may be related to cognitive decline. However, because this is a small phase 2 study, it is important for this or similar work to be done in larger, more diverse populations and over a longer duration of the intervention.” She was not involved with the study but was asked to comment.

Investigators chose the 20-week duration, they explained, because control-group patients likely would not refrain from trying the lifestyle intervention beyond that timeframe. Perhaps more importantly, challenges created by the COVID-19 pandemic required researchers to cut planned enrollment in half, eliminate planned MRI and amyloid PET scans, and reduce the number of cognition and function tests.

Such shortcomings limit what neurologists can glean and generalize from the study, said Dr. Snyder. “That said,” she added, “it does demonstrate the potential of an intensive behavior/lifestyle intervention, and the importance of this sort of research in Alzheimer’s and dementia.” Although the complexity of the interventions makes these studies challenging, she added, “it is important that we continue to advance larger, longer studies in more representative study populations to develop specific recommendations.”
 

Further Study

The Alzheimer’s Association’s U.S. POINTER study is the first large-scale study in the United States to explore the impact of comprehensive lifestyle changes on cognitive health. About 2000 older adults at risk for cognitive decline are participating, from diverse locations across the country. More than 25% of participants come from groups typically underrepresented in dementia research, said Dr. Snyder. Initial results are expected in summer 2025.

Future research also should explore reasons (beyond adherence) why some patients respond to lifestyle interventions better than others, and the potential synergy of lifestyle changes with drug therapies, wrote Dr. Ornish and colleagues.

“For now,” said Dr. Snyder, “there is an opportunity for providers to incorporate or expand messaging with their patients and families about the habits that they can incorporate into their daily lives. The Alzheimer’s Association offers 10 Healthy Habits for Your Brain — everyday actions that can make a difference for your brain health.”

Investigators received study funding from more than two dozen charitable foundations and other organizations. Dr. Snyder is a full-time employee of the Alzheimer’s Association and in this role, serves on the leadership team of the U.S. POINTER study. Her partner works for Abbott in an unrelated field. 

An intensive lifestyle intervention significantly improved cognition and function in many patients with mild cognitive impairment (MCI) or early dementia due to Alzheimer’s disease, in what authors said is the first randomized controlled trial of intensive lifestyle modification for patients diagnosed with Alzheimer’s disease. Results could help physicians address patients at risk of Alzheimer’s disease who reject relevant testing because they believe nothing can forestall development of the disease, the authors added. The study was published online in Alzheimer’s Research & Therapy.

Although technology allows probable Alzheimer’s disease diagnosis years before clinical symptoms appear, wrote investigators led by Dean Ornish, MD, of the Preventive Medicine Research Institute in Sausalito, California, “many people do not want to know if they are likely to get Alzheimer’s disease if they do not believe they can do anything about it. If intensive lifestyle changes may cause improvement in cognition and function in MCI or early dementia due to Alzheimer’s disease, then it is reasonable to think that these lifestyle changes may also help to prevent MCI or early dementia due to Alzheimer’s disease.” As with cardiovascular disease, the authors added, preventing Alzheimer’s disease might require less intensive lifestyle modifications than treating it.
 

Study Methodology

Investigators randomized 26 patients with Montréal Cognitive Assessment scores of 18 or higher to an intensive intervention involving nutrition, exercise, and stress management techniques. To improve adherence, the protocol included participants’ spouses or caregivers.

Two patients, both in the treatment group, withdrew over logistical concerns.

After 20 weeks, treated patients exhibited statistically significant differences in several key measures versus a 25-patient usual-care control group. Scores that improved in the intervention group and worsened among controls included the following:

• Clinical Global Impression of Change (CGIC, P = .001)
• Clinical Dementia Rating-Global (CDR-Global, -0.04, P = .037)
• Clinical Dementia Rating Sum of Boxes (CDR-SB, +0.08, P = .032)
• Alzheimer’s Disease Assessment Scale (ADAS-Cog, -1.01, P = .053)

The validity of these changes in cognition and function, and possible biological mechanisms of improvement, were supported by statistically significant improvements in several clinically relevant biomarkers versus controls, the investigators wrote. These biomarkers included Abeta42/40 ratio, HbA1c, insulin, and glycoprotein acetylation. “This information may also help in predicting which patients are more likely to show improvements in cognition and function by making these intensive lifestyle changes,” the authors added.

In primary analysis, the degree of lifestyle changes required to stop progression of MCI ranged from 71.4% (ADAS-Cog) to 120.6% (CDR-SB). “This helps to explain why other studies of less intensive lifestyle interventions may not have been sufficient to stop deterioration or improve cognition and function,” the authors wrote. Moreover, they added, variable adherence might explain why in the intervention group, 10 patients improved their CGIC scores, while the rest held static or worsened.
 

Caveats

Alzheimer’s Association Vice President of Medical and Scientific Relations Heather M. Snyder, PhD, said, “This is an interesting paper in an important area of research and adds to the growing body of literature on how behavior or lifestyle may be related to cognitive decline. However, because this is a small phase 2 study, it is important for this or similar work to be done in larger, more diverse populations and over a longer duration of the intervention.” She was not involved with the study but was asked to comment.

Investigators chose the 20-week duration, they explained, because control-group patients likely would not refrain from trying the lifestyle intervention beyond that timeframe. Perhaps more importantly, challenges created by the COVID-19 pandemic required researchers to cut planned enrollment in half, eliminate planned MRI and amyloid PET scans, and reduce the number of cognition and function tests.

Such shortcomings limit what neurologists can glean and generalize from the study, said Dr. Snyder. “That said,” she added, “it does demonstrate the potential of an intensive behavior/lifestyle intervention, and the importance of this sort of research in Alzheimer’s and dementia.” Although the complexity of the interventions makes these studies challenging, she added, “it is important that we continue to advance larger, longer studies in more representative study populations to develop specific recommendations.”
 

Further Study

The Alzheimer’s Association’s U.S. POINTER study is the first large-scale study in the United States to explore the impact of comprehensive lifestyle changes on cognitive health. About 2000 older adults at risk for cognitive decline are participating, from diverse locations across the country. More than 25% of participants come from groups typically underrepresented in dementia research, said Dr. Snyder. Initial results are expected in summer 2025.

Future research also should explore reasons (beyond adherence) why some patients respond to lifestyle interventions better than others, and the potential synergy of lifestyle changes with drug therapies, wrote Dr. Ornish and colleagues.

“For now,” said Dr. Snyder, “there is an opportunity for providers to incorporate or expand messaging with their patients and families about the habits that they can incorporate into their daily lives. The Alzheimer’s Association offers 10 Healthy Habits for Your Brain — everyday actions that can make a difference for your brain health.”

Investigators received study funding from more than two dozen charitable foundations and other organizations. Dr. Snyder is a full-time employee of the Alzheimer’s Association and in this role, serves on the leadership team of the U.S. POINTER study. Her partner works for Abbott in an unrelated field. 

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article appeared on Medscape.com.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article appeared on Medscape.com.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article appeared on Medscape.com.

SAN DIEGO — In a randomized, controlled trial, lidocaine injections to the greater occipital nerve were effective in controlling migraine symptoms among adolescents. The treatment has long been used in adults, and frequently in children on the strength of observational evidence.

Prior Research

Most of the studies have been conducted in adults, and these were often in specific settings like the emergency department for status migrainosus, while outpatient studies were generally conducted in chronic migraine, according to presenting author Christina Szperka, MD. “The assumptions were a little bit different,” Dr. Szperka, director of the pediatric headache program at Children’s Hospital of Philadelphia, said in an interview.

Retrospective studies are also fraught with bias. “We’ve tried to look at retrospective data. People don’t necessarily report how they’re doing unless they come back, and so you lose a huge portion of kids,” said Dr. Szperka, who presented the research at the annual meeting of the American Headache Society.

“From a clinical perspective, I think it gives us additional evidence that what we’re doing makes a difference, and I think that will help us in terms of insurance coverage, because that’s really been a major barrier,” said Dr. Szperka.

The study also opens other avenues for research. “Just doing the greater occipital nerves only reduces the pain so much. So what’s the next step? Do I study additional injections? Do I do a study where I compare different medications?”

She previously conducted a study of how providers were using lidocaine injections, and “there was a large amount of variability, both in terms of what nerves are being injected, what medications they were using, the patient population, et cetera,” said Dr. Szperka. Previous observational studies have suggested efficacy in pediatric populations for transition and prevention of migraine, new daily persistent headache, posttraumatic headache, and post-shunt occipital neuralgia.
 

A Randomized, Controlled Trial

In the new study, 58 adolescents aged 7 to 21 (mean age, 16.0 years; 44 female) were initially treated with lidocaine cream. The patients were “relatively refractory,” said Dr. Szperka, with 25 having received intravenous medications and 6 having been inpatients. After 30 minutes, if they still had pain and consented to further treatment, Dr. Szperka performed bilateral greater occipital nerve injections with lidocaine or a saline placebo, and did additional injections after 30 minutes if there wasn’t sufficient improvement.

There was no significant change in pain after the lidocaine cream treatment, and all patients proceeded to be randomized to lidocaine or placebo injections. The primary outcome of 30-minute reduction in pain score ranked 0-10 favored the lidocaine group (2.3 vs 1.1; P = .013). There was a 2-point reduction in pain scores in 69% of the lidocaine group and 34% of the saline group (P = .009) and a higher frequency of pain relief from moderate/severe to no pain or mild (52% versus 24%; P = .03). There was no significant difference in pain freedom.

After 24 hours, the treatment group was more likely to experience pain relief from moderate/severe to no pain or mild (24% vs 3%; P = .05) and to be free from associated symptoms (48% vs 21%; P = .027). Pain at the injection site was significantly higher in the placebo group (5.4 vs 3.2), prompting a change in plans for future trials. “I don’t think I would do saline again, because I think it hurt them, and I don’t want to cause them harm,” said Dr. Szperka.

Adverse events were common, with all but one patient in the study experiencing at least one. “I think this is a couple of things: One, kids don’t like needles in their head. Nerve blocks hurt. And so it was not surprising in some ways that we had a very high rate of adverse events. We also consented them, and that had a long wait period, and there’s a lot of anxiety in the room. However, most of the adverse events were mild,” said Dr. Szperka.
 

Important Research in an Understudied Population

Laine Greene, MD, who moderated the session, was asked for comment. “I think it’s an important study. Occipital nerve blocks have been used for a long period of time in management of migraine and other headache disorders. The quality of the evidence has always been brought into question, especially from payers, but also a very important aspect to this is that a lot of clinical trials over time have not specifically been done in children or adolescents, so any work that is done in that age category is significantly helpful to advancing therapeutics,” said Dr. Greene, associate professor of neurology at Mayo Clinic Arizona.

Dr. Szperka has consulted for AbbVie and Teva, and serves on data safety and monitoring boards for Eli Lilly and Upsher-Smith. She has been a principal investigator in trials sponsored by Abbvie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Greene has no relevant financial disclosures.

SAN DIEGO — In a randomized, controlled trial, lidocaine injections to the greater occipital nerve were effective in controlling migraine symptoms among adolescents. The treatment has long been used in adults, and frequently in children on the strength of observational evidence.

Prior Research

Most of the studies have been conducted in adults, and these were often in specific settings like the emergency department for status migrainosus, while outpatient studies were generally conducted in chronic migraine, according to presenting author Christina Szperka, MD. “The assumptions were a little bit different,” Dr. Szperka, director of the pediatric headache program at Children’s Hospital of Philadelphia, said in an interview.

Retrospective studies are also fraught with bias. “We’ve tried to look at retrospective data. People don’t necessarily report how they’re doing unless they come back, and so you lose a huge portion of kids,” said Dr. Szperka, who presented the research at the annual meeting of the American Headache Society.

“From a clinical perspective, I think it gives us additional evidence that what we’re doing makes a difference, and I think that will help us in terms of insurance coverage, because that’s really been a major barrier,” said Dr. Szperka.

The study also opens other avenues for research. “Just doing the greater occipital nerves only reduces the pain so much. So what’s the next step? Do I study additional injections? Do I do a study where I compare different medications?”

She previously conducted a study of how providers were using lidocaine injections, and “there was a large amount of variability, both in terms of what nerves are being injected, what medications they were using, the patient population, et cetera,” said Dr. Szperka. Previous observational studies have suggested efficacy in pediatric populations for transition and prevention of migraine, new daily persistent headache, posttraumatic headache, and post-shunt occipital neuralgia.
 

A Randomized, Controlled Trial

In the new study, 58 adolescents aged 7 to 21 (mean age, 16.0 years; 44 female) were initially treated with lidocaine cream. The patients were “relatively refractory,” said Dr. Szperka, with 25 having received intravenous medications and 6 having been inpatients. After 30 minutes, if they still had pain and consented to further treatment, Dr. Szperka performed bilateral greater occipital nerve injections with lidocaine or a saline placebo, and did additional injections after 30 minutes if there wasn’t sufficient improvement.

There was no significant change in pain after the lidocaine cream treatment, and all patients proceeded to be randomized to lidocaine or placebo injections. The primary outcome of 30-minute reduction in pain score ranked 0-10 favored the lidocaine group (2.3 vs 1.1; P = .013). There was a 2-point reduction in pain scores in 69% of the lidocaine group and 34% of the saline group (P = .009) and a higher frequency of pain relief from moderate/severe to no pain or mild (52% versus 24%; P = .03). There was no significant difference in pain freedom.

After 24 hours, the treatment group was more likely to experience pain relief from moderate/severe to no pain or mild (24% vs 3%; P = .05) and to be free from associated symptoms (48% vs 21%; P = .027). Pain at the injection site was significantly higher in the placebo group (5.4 vs 3.2), prompting a change in plans for future trials. “I don’t think I would do saline again, because I think it hurt them, and I don’t want to cause them harm,” said Dr. Szperka.

Adverse events were common, with all but one patient in the study experiencing at least one. “I think this is a couple of things: One, kids don’t like needles in their head. Nerve blocks hurt. And so it was not surprising in some ways that we had a very high rate of adverse events. We also consented them, and that had a long wait period, and there’s a lot of anxiety in the room. However, most of the adverse events were mild,” said Dr. Szperka.
 

Important Research in an Understudied Population

Laine Greene, MD, who moderated the session, was asked for comment. “I think it’s an important study. Occipital nerve blocks have been used for a long period of time in management of migraine and other headache disorders. The quality of the evidence has always been brought into question, especially from payers, but also a very important aspect to this is that a lot of clinical trials over time have not specifically been done in children or adolescents, so any work that is done in that age category is significantly helpful to advancing therapeutics,” said Dr. Greene, associate professor of neurology at Mayo Clinic Arizona.

Dr. Szperka has consulted for AbbVie and Teva, and serves on data safety and monitoring boards for Eli Lilly and Upsher-Smith. She has been a principal investigator in trials sponsored by Abbvie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Greene has no relevant financial disclosures.

SAN DIEGO — In a randomized, controlled trial, lidocaine injections to the greater occipital nerve were effective in controlling migraine symptoms among adolescents. The treatment has long been used in adults, and frequently in children on the strength of observational evidence.

Prior Research

Most of the studies have been conducted in adults, and these were often in specific settings like the emergency department for status migrainosus, while outpatient studies were generally conducted in chronic migraine, according to presenting author Christina Szperka, MD. “The assumptions were a little bit different,” Dr. Szperka, director of the pediatric headache program at Children’s Hospital of Philadelphia, said in an interview.

Retrospective studies are also fraught with bias. “We’ve tried to look at retrospective data. People don’t necessarily report how they’re doing unless they come back, and so you lose a huge portion of kids,” said Dr. Szperka, who presented the research at the annual meeting of the American Headache Society.

“From a clinical perspective, I think it gives us additional evidence that what we’re doing makes a difference, and I think that will help us in terms of insurance coverage, because that’s really been a major barrier,” said Dr. Szperka.

The study also opens other avenues for research. “Just doing the greater occipital nerves only reduces the pain so much. So what’s the next step? Do I study additional injections? Do I do a study where I compare different medications?”

She previously conducted a study of how providers were using lidocaine injections, and “there was a large amount of variability, both in terms of what nerves are being injected, what medications they were using, the patient population, et cetera,” said Dr. Szperka. Previous observational studies have suggested efficacy in pediatric populations for transition and prevention of migraine, new daily persistent headache, posttraumatic headache, and post-shunt occipital neuralgia.
 

A Randomized, Controlled Trial

In the new study, 58 adolescents aged 7 to 21 (mean age, 16.0 years; 44 female) were initially treated with lidocaine cream. The patients were “relatively refractory,” said Dr. Szperka, with 25 having received intravenous medications and 6 having been inpatients. After 30 minutes, if they still had pain and consented to further treatment, Dr. Szperka performed bilateral greater occipital nerve injections with lidocaine or a saline placebo, and did additional injections after 30 minutes if there wasn’t sufficient improvement.

There was no significant change in pain after the lidocaine cream treatment, and all patients proceeded to be randomized to lidocaine or placebo injections. The primary outcome of 30-minute reduction in pain score ranked 0-10 favored the lidocaine group (2.3 vs 1.1; P = .013). There was a 2-point reduction in pain scores in 69% of the lidocaine group and 34% of the saline group (P = .009) and a higher frequency of pain relief from moderate/severe to no pain or mild (52% versus 24%; P = .03). There was no significant difference in pain freedom.

After 24 hours, the treatment group was more likely to experience pain relief from moderate/severe to no pain or mild (24% vs 3%; P = .05) and to be free from associated symptoms (48% vs 21%; P = .027). Pain at the injection site was significantly higher in the placebo group (5.4 vs 3.2), prompting a change in plans for future trials. “I don’t think I would do saline again, because I think it hurt them, and I don’t want to cause them harm,” said Dr. Szperka.

Adverse events were common, with all but one patient in the study experiencing at least one. “I think this is a couple of things: One, kids don’t like needles in their head. Nerve blocks hurt. And so it was not surprising in some ways that we had a very high rate of adverse events. We also consented them, and that had a long wait period, and there’s a lot of anxiety in the room. However, most of the adverse events were mild,” said Dr. Szperka.
 

Important Research in an Understudied Population

Laine Greene, MD, who moderated the session, was asked for comment. “I think it’s an important study. Occipital nerve blocks have been used for a long period of time in management of migraine and other headache disorders. The quality of the evidence has always been brought into question, especially from payers, but also a very important aspect to this is that a lot of clinical trials over time have not specifically been done in children or adolescents, so any work that is done in that age category is significantly helpful to advancing therapeutics,” said Dr. Greene, associate professor of neurology at Mayo Clinic Arizona.

Dr. Szperka has consulted for AbbVie and Teva, and serves on data safety and monitoring boards for Eli Lilly and Upsher-Smith. She has been a principal investigator in trials sponsored by Abbvie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Greene has no relevant financial disclosures.

Using combined genetic testing in early childhood may decrease the misdiagnosis rate for Global Development Delay (GDD) and may help identify intervention targets, a new study suggests.

Researchers, led by Jiamei Zhang, MS, Department of Rehabilitation Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China, in a multicenter, prospective cohort study enrolled patients ages 12 to 60 months with GDD from six centers in China from July 2020 through August 2023. Participants underwent trio whole exome sequencing (trio-WES) paired with copy number variation sequencing (CNV-seq).

“To the best of our knowledge, this study represents the largest prospective examination of combined genetic testing methods in a GDD cohort,” the authors reported in JAMA Network Open.

GDD is a common neurodevelopmental disorder, marked by cognitive impairment, and affects about 1% of children, the paper states. Most children with GDD develop intellectual disability (ID) after 5 years of age, with implications for quality of life, their physical abilities, and social functioning. Early and accurate diagnosis followed by appropriately targeted treatment is critical, but lacking. Researchers note that there is lack of consensus among health care professionals on whether genetic testing is necessary.

Genetics are known to play a significant role in pathogenesis of GDD, but definitive biomarkers have been elusive.
 

Positive Detection Rate of 61%

In this study, the combined use of trio-WES with CNV-seq in children with early-stage GDD resulted in a positive detection rate of 61%, a significant improvement over performing individual tests, “enhancing the positive detection rate by 18%-40%,” the researchers wrote. The combined approach also saves families time and costs, they note, while leading to more comprehensive genetic analysis and fewer missed diagnoses.

The combined approach also addressed the limitations of trio-WES and CNV-seq used alone, the authors wrote. Because of technological constraints, trio-WES may miss 55% of CNV variations, and CNV-seq has a missed diagnosis rate of 3%.

The study included 434 patients with GDD (60% male; average age, 25 months) with diverse degrees of cognitive impairment: mild (23%); moderate (32%); severe (28%); and profound (17%).

Three characteristics were linked with higher likelihood of having genetic variants: Craniofacial abnormalities (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.45-3.56); moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70); and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35).
 

Dopaminergic Pathway Promising for Treatment

Researchers also discovered that GDD-related genes were primarily enriched in lysosome, dopaminergic synapse, and lysine degradation pathways. Dopaminergic synapse emerged as a significant pathway linked with GDD.

“In this cohort study, our findings support the correlation between dopaminergic synapse and cognitive impairment, as substantiated by prior research and animal models. Therefore, targeting the dopaminergic pathway holds promise for treating GDD and ID,” the authors wrote.

However, the authors note in the limitations that they used only a subset of 100 patients with GDD to measure dopamine concentration.

“Expanding the sample size and conducting in vivo and in vitro experiments are necessary steps to verify whether dopamine can be targeted for clinical precision medical intervention in patients with GDD,” they wrote.

The authors reported no relevant financial relationships.

Using combined genetic testing in early childhood may decrease the misdiagnosis rate for Global Development Delay (GDD) and may help identify intervention targets, a new study suggests.

Researchers, led by Jiamei Zhang, MS, Department of Rehabilitation Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China, in a multicenter, prospective cohort study enrolled patients ages 12 to 60 months with GDD from six centers in China from July 2020 through August 2023. Participants underwent trio whole exome sequencing (trio-WES) paired with copy number variation sequencing (CNV-seq).

“To the best of our knowledge, this study represents the largest prospective examination of combined genetic testing methods in a GDD cohort,” the authors reported in JAMA Network Open.

GDD is a common neurodevelopmental disorder, marked by cognitive impairment, and affects about 1% of children, the paper states. Most children with GDD develop intellectual disability (ID) after 5 years of age, with implications for quality of life, their physical abilities, and social functioning. Early and accurate diagnosis followed by appropriately targeted treatment is critical, but lacking. Researchers note that there is lack of consensus among health care professionals on whether genetic testing is necessary.

Genetics are known to play a significant role in pathogenesis of GDD, but definitive biomarkers have been elusive.
 

Positive Detection Rate of 61%

In this study, the combined use of trio-WES with CNV-seq in children with early-stage GDD resulted in a positive detection rate of 61%, a significant improvement over performing individual tests, “enhancing the positive detection rate by 18%-40%,” the researchers wrote. The combined approach also saves families time and costs, they note, while leading to more comprehensive genetic analysis and fewer missed diagnoses.

The combined approach also addressed the limitations of trio-WES and CNV-seq used alone, the authors wrote. Because of technological constraints, trio-WES may miss 55% of CNV variations, and CNV-seq has a missed diagnosis rate of 3%.

The study included 434 patients with GDD (60% male; average age, 25 months) with diverse degrees of cognitive impairment: mild (23%); moderate (32%); severe (28%); and profound (17%).

Three characteristics were linked with higher likelihood of having genetic variants: Craniofacial abnormalities (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.45-3.56); moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70); and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35).
 

Dopaminergic Pathway Promising for Treatment

Researchers also discovered that GDD-related genes were primarily enriched in lysosome, dopaminergic synapse, and lysine degradation pathways. Dopaminergic synapse emerged as a significant pathway linked with GDD.

“In this cohort study, our findings support the correlation between dopaminergic synapse and cognitive impairment, as substantiated by prior research and animal models. Therefore, targeting the dopaminergic pathway holds promise for treating GDD and ID,” the authors wrote.

However, the authors note in the limitations that they used only a subset of 100 patients with GDD to measure dopamine concentration.

“Expanding the sample size and conducting in vivo and in vitro experiments are necessary steps to verify whether dopamine can be targeted for clinical precision medical intervention in patients with GDD,” they wrote.

The authors reported no relevant financial relationships.

Using combined genetic testing in early childhood may decrease the misdiagnosis rate for Global Development Delay (GDD) and may help identify intervention targets, a new study suggests.

Researchers, led by Jiamei Zhang, MS, Department of Rehabilitation Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China, in a multicenter, prospective cohort study enrolled patients ages 12 to 60 months with GDD from six centers in China from July 2020 through August 2023. Participants underwent trio whole exome sequencing (trio-WES) paired with copy number variation sequencing (CNV-seq).

“To the best of our knowledge, this study represents the largest prospective examination of combined genetic testing methods in a GDD cohort,” the authors reported in JAMA Network Open.

GDD is a common neurodevelopmental disorder, marked by cognitive impairment, and affects about 1% of children, the paper states. Most children with GDD develop intellectual disability (ID) after 5 years of age, with implications for quality of life, their physical abilities, and social functioning. Early and accurate diagnosis followed by appropriately targeted treatment is critical, but lacking. Researchers note that there is lack of consensus among health care professionals on whether genetic testing is necessary.

Genetics are known to play a significant role in pathogenesis of GDD, but definitive biomarkers have been elusive.
 

Positive Detection Rate of 61%

In this study, the combined use of trio-WES with CNV-seq in children with early-stage GDD resulted in a positive detection rate of 61%, a significant improvement over performing individual tests, “enhancing the positive detection rate by 18%-40%,” the researchers wrote. The combined approach also saves families time and costs, they note, while leading to more comprehensive genetic analysis and fewer missed diagnoses.

The combined approach also addressed the limitations of trio-WES and CNV-seq used alone, the authors wrote. Because of technological constraints, trio-WES may miss 55% of CNV variations, and CNV-seq has a missed diagnosis rate of 3%.

The study included 434 patients with GDD (60% male; average age, 25 months) with diverse degrees of cognitive impairment: mild (23%); moderate (32%); severe (28%); and profound (17%).

Three characteristics were linked with higher likelihood of having genetic variants: Craniofacial abnormalities (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.45-3.56); moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70); and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35).
 

Dopaminergic Pathway Promising for Treatment

Researchers also discovered that GDD-related genes were primarily enriched in lysosome, dopaminergic synapse, and lysine degradation pathways. Dopaminergic synapse emerged as a significant pathway linked with GDD.

“In this cohort study, our findings support the correlation between dopaminergic synapse and cognitive impairment, as substantiated by prior research and animal models. Therefore, targeting the dopaminergic pathway holds promise for treating GDD and ID,” the authors wrote.

However, the authors note in the limitations that they used only a subset of 100 patients with GDD to measure dopamine concentration.

“Expanding the sample size and conducting in vivo and in vitro experiments are necessary steps to verify whether dopamine can be targeted for clinical precision medical intervention in patients with GDD,” they wrote.

The authors reported no relevant financial relationships.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

A version of this article first appeared on Medscape.com.

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

A version of this article first appeared on Medscape.com.

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

A version of this article first appeared on Medscape.com.

After 26 years in practice, there are still things about the brain that amaze me, often that I first notice on myself.

Filtering (I guess “selective attention” sounds better) is one of them. We don’t notice it, but it’s definitely there.

Working at a jigsaw puzzle, I find myself looking for a specific piece, say, a white tab with a dark background and yellow stripe in the center. There may be several hundred pieces spread around me at the table, but the brain quickly starts filtering them out. In a fraction of a second I only notice ones with a white tab, then mentally those are broken down by the other characteristics. If it looks promising, I’ll look back at the space I’m trying to fit it in, mentally rotate the piece (another tricky thing if you think about it) and, if that seems to match, will pick up the piece to try. If it doesn’t fit the process repeats.

It’s a remarkable ability to see a relationship between two separate objects that isn’t always apparent.

But it’s not just sight. Although I’ve always loved music, it wasn’t until my own kids were in a band that I found the ability to break it down, removing the other instruments. It brings a remarkable clarity to suddenly hearing my daughter on the marimba, or son on the flute. Even with 70 other instrument playing around them.

You can try it yourself, listening to Keith Moon’s amazing drums on The Who’s “5:15.” Or in Bob Seger’s “Fire Lake.” Take out Seger and the instruments and you suddenly realize it’s the Eagles doing the background singing.

In Carly Simon’s “You’re So Vain,” a song you generally don’t attribute to the Rolling Stones, a little bit of focus will reveal Mick Jagger’s distinctive voice in the background chorus of “Don’t you, don’t you, don’t you?”

The ability isn’t something we created. It was there from our ancestors in the trees and caves. They used this ability to identify friend from foe, find the right path home, and pick out what was edible from what was poisonous. Like with so many other things, and without realizing it, our brains have retooled it for the world we now face, even if it’s just to find our car in the parking lot.

Sodium, calcium, potassium, and other ions flow in and out of nerve cells, an electrical impulse propagates though a network, matching incoming sounds and images to ones previously stored. That’s all it is, but the results are remarkable.

We take the everyday for granted, but should stop and think how amazing it really is.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

After 26 years in practice, there are still things about the brain that amaze me, often that I first notice on myself.

Filtering (I guess “selective attention” sounds better) is one of them. We don’t notice it, but it’s definitely there.

Working at a jigsaw puzzle, I find myself looking for a specific piece, say, a white tab with a dark background and yellow stripe in the center. There may be several hundred pieces spread around me at the table, but the brain quickly starts filtering them out. In a fraction of a second I only notice ones with a white tab, then mentally those are broken down by the other characteristics. If it looks promising, I’ll look back at the space I’m trying to fit it in, mentally rotate the piece (another tricky thing if you think about it) and, if that seems to match, will pick up the piece to try. If it doesn’t fit the process repeats.

It’s a remarkable ability to see a relationship between two separate objects that isn’t always apparent.

But it’s not just sight. Although I’ve always loved music, it wasn’t until my own kids were in a band that I found the ability to break it down, removing the other instruments. It brings a remarkable clarity to suddenly hearing my daughter on the marimba, or son on the flute. Even with 70 other instrument playing around them.

You can try it yourself, listening to Keith Moon’s amazing drums on The Who’s “5:15.” Or in Bob Seger’s “Fire Lake.” Take out Seger and the instruments and you suddenly realize it’s the Eagles doing the background singing.

In Carly Simon’s “You’re So Vain,” a song you generally don’t attribute to the Rolling Stones, a little bit of focus will reveal Mick Jagger’s distinctive voice in the background chorus of “Don’t you, don’t you, don’t you?”

The ability isn’t something we created. It was there from our ancestors in the trees and caves. They used this ability to identify friend from foe, find the right path home, and pick out what was edible from what was poisonous. Like with so many other things, and without realizing it, our brains have retooled it for the world we now face, even if it’s just to find our car in the parking lot.

Sodium, calcium, potassium, and other ions flow in and out of nerve cells, an electrical impulse propagates though a network, matching incoming sounds and images to ones previously stored. That’s all it is, but the results are remarkable.

We take the everyday for granted, but should stop and think how amazing it really is.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

After 26 years in practice, there are still things about the brain that amaze me, often that I first notice on myself.

Filtering (I guess “selective attention” sounds better) is one of them. We don’t notice it, but it’s definitely there.

Working at a jigsaw puzzle, I find myself looking for a specific piece, say, a white tab with a dark background and yellow stripe in the center. There may be several hundred pieces spread around me at the table, but the brain quickly starts filtering them out. In a fraction of a second I only notice ones with a white tab, then mentally those are broken down by the other characteristics. If it looks promising, I’ll look back at the space I’m trying to fit it in, mentally rotate the piece (another tricky thing if you think about it) and, if that seems to match, will pick up the piece to try. If it doesn’t fit the process repeats.

It’s a remarkable ability to see a relationship between two separate objects that isn’t always apparent.

But it’s not just sight. Although I’ve always loved music, it wasn’t until my own kids were in a band that I found the ability to break it down, removing the other instruments. It brings a remarkable clarity to suddenly hearing my daughter on the marimba, or son on the flute. Even with 70 other instrument playing around them.

You can try it yourself, listening to Keith Moon’s amazing drums on The Who’s “5:15.” Or in Bob Seger’s “Fire Lake.” Take out Seger and the instruments and you suddenly realize it’s the Eagles doing the background singing.

In Carly Simon’s “You’re So Vain,” a song you generally don’t attribute to the Rolling Stones, a little bit of focus will reveal Mick Jagger’s distinctive voice in the background chorus of “Don’t you, don’t you, don’t you?”

The ability isn’t something we created. It was there from our ancestors in the trees and caves. They used this ability to identify friend from foe, find the right path home, and pick out what was edible from what was poisonous. Like with so many other things, and without realizing it, our brains have retooled it for the world we now face, even if it’s just to find our car in the parking lot.

Sodium, calcium, potassium, and other ions flow in and out of nerve cells, an electrical impulse propagates though a network, matching incoming sounds and images to ones previously stored. That’s all it is, but the results are remarkable.

We take the everyday for granted, but should stop and think how amazing it really is.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

SAN DIEGO — Susceptibility to post-traumatic headache could be linked to mutations in ion channel and ion transporter genes, according to results from a preliminary study.

Post-traumatic headache is a common symptom of traumatic brain injury (TBI).

There is evidence that genetic mutations could play a role in both TBI development and response. In particular, the S213L mutation for familial hemiplegic migraine-1 (FHM1), found in the CACNA1A gene, can cause individuals carrying it to be highly sensitive to otherwise trivial head impacts, according to Lyn Griffiths, PhD.

The consequences can be post-traumatic headache, but also seizures, cerebral edema, coma, or worse. Another form of FHM is associated with mutations in ATP1A2.

“This stimulated our interest in looking at genes that relate to TBI with a particular focus on ion channel genes,” said Dr. Griffiths, during a presentation of the study at the annual meeting of the American Headache Society.

The researchers analyzed data from 117 participants who had at least one concussion with a post-traumatic headache, and recruited family members when possible. There were 15 participants who developed severe reactions to trivial head trauma, 13 who had been diagnosed with concussion and underwent imaging related to TBI-associated symptoms, 54 who had been recruited through local sporting groups campuses, and 35 recruited through a medical research foundation. Blood or saliva samples were used to perform whole exome sequencing.

The researchers looked for gene candidates within different tiers. Tier 1 included genes that had already been implicated in severe migraine. The second tier included 353 ion channel and iron transporter genes. Tier 3 comprised neurotransmission-related genes.

After sequencing, the researchers filtered genetic mutations to include only those that affected amino acid composition of the protein, were predicted by two or more in silico analysis tools to be damaging, and were identified in multiple, unrelated patients.

In tier 2, the greatest number of potential damaging variants were found in the SCN9A gene, which is involved in pain perception and processing. There were six variants found in eight cases. Of these eight individuals, three had suffered severe reactions to relatively minor head trauma.

In tier 3, the researchers identified mutations in eight neurotransmitter-related genes.

Through comparison with a general population control group, the researchers identified 43 different rare, amino acid–changing variants that occurred within 16 ion channel and ion channel transporter genes. These mutations were found in 53 individuals, at an approximately fivefold higher frequency than the control group (odds ratio, 5.6; P < .0001).

“We identified a number of rare genetic variants implicated in migraine — ion channel and other neurologically associated genes — in those suffering from post-traumatic headache,” said Dr. Griffiths. She also noted that the whole genomes they collected will allow for further analysis of other gene candidates in the future.

During the Q&A period, Dr. Griffiths was asked if the research group tracked the severity of the TBIs suffered by participants. She responded that they had not, and this was a limitation of the study.

Another questioner asked if parents should consider genetic testing for susceptibility mutations when considering whether to allow a child to participate in sports or activities with elevated risk of TBI. “I don’t necessarily think this is a bad thing,” she said, though she conceded that the work is still immature. “It’s probably a bit early because we haven’t identified all the genes that are involved or all the specific mutations ... but I think down the track, that makes perfect sense. Why would you not do some sensible preventive screening to aid with things like maybe you wear more headgear or you consider what’s the appropriate sport for that person?”

Laine Green, MD, assistant professor of neurology at Mayo Clinic Arizona, Phoenix, who moderated the session, was asked for comment. “I think the idea of potentially identifying people that have more genetic susceptibility to injuries is very intriguing, because post-traumatic headache and symptoms is always a difficult area to treat, potentially identifying those that with more genetic susceptibility might be helpful. It may also potentially allow us to target specific treatments, especially in this case, looking at different ion channels. There are medications that may work better at ion channel targets than other targets,” said Dr. Green.

He also endorsed the potential value of screening. “Speaking as a parent, I might like to know my child is at higher risk if they’re going to participate in contact sports or other high risk activities,” he said.

Dr. Griffiths and Dr. Green have no relevant financial disclosures.

SAN DIEGO — Susceptibility to post-traumatic headache could be linked to mutations in ion channel and ion transporter genes, according to results from a preliminary study.

Post-traumatic headache is a common symptom of traumatic brain injury (TBI).

There is evidence that genetic mutations could play a role in both TBI development and response. In particular, the S213L mutation for familial hemiplegic migraine-1 (FHM1), found in the CACNA1A gene, can cause individuals carrying it to be highly sensitive to otherwise trivial head impacts, according to Lyn Griffiths, PhD.

The consequences can be post-traumatic headache, but also seizures, cerebral edema, coma, or worse. Another form of FHM is associated with mutations in ATP1A2.

“This stimulated our interest in looking at genes that relate to TBI with a particular focus on ion channel genes,” said Dr. Griffiths, during a presentation of the study at the annual meeting of the American Headache Society.

The researchers analyzed data from 117 participants who had at least one concussion with a post-traumatic headache, and recruited family members when possible. There were 15 participants who developed severe reactions to trivial head trauma, 13 who had been diagnosed with concussion and underwent imaging related to TBI-associated symptoms, 54 who had been recruited through local sporting groups campuses, and 35 recruited through a medical research foundation. Blood or saliva samples were used to perform whole exome sequencing.

The researchers looked for gene candidates within different tiers. Tier 1 included genes that had already been implicated in severe migraine. The second tier included 353 ion channel and iron transporter genes. Tier 3 comprised neurotransmission-related genes.

After sequencing, the researchers filtered genetic mutations to include only those that affected amino acid composition of the protein, were predicted by two or more in silico analysis tools to be damaging, and were identified in multiple, unrelated patients.

In tier 2, the greatest number of potential damaging variants were found in the SCN9A gene, which is involved in pain perception and processing. There were six variants found in eight cases. Of these eight individuals, three had suffered severe reactions to relatively minor head trauma.

In tier 3, the researchers identified mutations in eight neurotransmitter-related genes.

Through comparison with a general population control group, the researchers identified 43 different rare, amino acid–changing variants that occurred within 16 ion channel and ion channel transporter genes. These mutations were found in 53 individuals, at an approximately fivefold higher frequency than the control group (odds ratio, 5.6; P < .0001).

“We identified a number of rare genetic variants implicated in migraine — ion channel and other neurologically associated genes — in those suffering from post-traumatic headache,” said Dr. Griffiths. She also noted that the whole genomes they collected will allow for further analysis of other gene candidates in the future.

During the Q&A period, Dr. Griffiths was asked if the research group tracked the severity of the TBIs suffered by participants. She responded that they had not, and this was a limitation of the study.

Another questioner asked if parents should consider genetic testing for susceptibility mutations when considering whether to allow a child to participate in sports or activities with elevated risk of TBI. “I don’t necessarily think this is a bad thing,” she said, though she conceded that the work is still immature. “It’s probably a bit early because we haven’t identified all the genes that are involved or all the specific mutations ... but I think down the track, that makes perfect sense. Why would you not do some sensible preventive screening to aid with things like maybe you wear more headgear or you consider what’s the appropriate sport for that person?”

Laine Green, MD, assistant professor of neurology at Mayo Clinic Arizona, Phoenix, who moderated the session, was asked for comment. “I think the idea of potentially identifying people that have more genetic susceptibility to injuries is very intriguing, because post-traumatic headache and symptoms is always a difficult area to treat, potentially identifying those that with more genetic susceptibility might be helpful. It may also potentially allow us to target specific treatments, especially in this case, looking at different ion channels. There are medications that may work better at ion channel targets than other targets,” said Dr. Green.

He also endorsed the potential value of screening. “Speaking as a parent, I might like to know my child is at higher risk if they’re going to participate in contact sports or other high risk activities,” he said.

Dr. Griffiths and Dr. Green have no relevant financial disclosures.

SAN DIEGO — Susceptibility to post-traumatic headache could be linked to mutations in ion channel and ion transporter genes, according to results from a preliminary study.

Post-traumatic headache is a common symptom of traumatic brain injury (TBI).

There is evidence that genetic mutations could play a role in both TBI development and response. In particular, the S213L mutation for familial hemiplegic migraine-1 (FHM1), found in the CACNA1A gene, can cause individuals carrying it to be highly sensitive to otherwise trivial head impacts, according to Lyn Griffiths, PhD.

The consequences can be post-traumatic headache, but also seizures, cerebral edema, coma, or worse. Another form of FHM is associated with mutations in ATP1A2.

“This stimulated our interest in looking at genes that relate to TBI with a particular focus on ion channel genes,” said Dr. Griffiths, during a presentation of the study at the annual meeting of the American Headache Society.

The researchers analyzed data from 117 participants who had at least one concussion with a post-traumatic headache, and recruited family members when possible. There were 15 participants who developed severe reactions to trivial head trauma, 13 who had been diagnosed with concussion and underwent imaging related to TBI-associated symptoms, 54 who had been recruited through local sporting groups campuses, and 35 recruited through a medical research foundation. Blood or saliva samples were used to perform whole exome sequencing.

The researchers looked for gene candidates within different tiers. Tier 1 included genes that had already been implicated in severe migraine. The second tier included 353 ion channel and iron transporter genes. Tier 3 comprised neurotransmission-related genes.

After sequencing, the researchers filtered genetic mutations to include only those that affected amino acid composition of the protein, were predicted by two or more in silico analysis tools to be damaging, and were identified in multiple, unrelated patients.

In tier 2, the greatest number of potential damaging variants were found in the SCN9A gene, which is involved in pain perception and processing. There were six variants found in eight cases. Of these eight individuals, three had suffered severe reactions to relatively minor head trauma.

In tier 3, the researchers identified mutations in eight neurotransmitter-related genes.

Through comparison with a general population control group, the researchers identified 43 different rare, amino acid–changing variants that occurred within 16 ion channel and ion channel transporter genes. These mutations were found in 53 individuals, at an approximately fivefold higher frequency than the control group (odds ratio, 5.6; P < .0001).

“We identified a number of rare genetic variants implicated in migraine — ion channel and other neurologically associated genes — in those suffering from post-traumatic headache,” said Dr. Griffiths. She also noted that the whole genomes they collected will allow for further analysis of other gene candidates in the future.

During the Q&A period, Dr. Griffiths was asked if the research group tracked the severity of the TBIs suffered by participants. She responded that they had not, and this was a limitation of the study.

Another questioner asked if parents should consider genetic testing for susceptibility mutations when considering whether to allow a child to participate in sports or activities with elevated risk of TBI. “I don’t necessarily think this is a bad thing,” she said, though she conceded that the work is still immature. “It’s probably a bit early because we haven’t identified all the genes that are involved or all the specific mutations ... but I think down the track, that makes perfect sense. Why would you not do some sensible preventive screening to aid with things like maybe you wear more headgear or you consider what’s the appropriate sport for that person?”

Laine Green, MD, assistant professor of neurology at Mayo Clinic Arizona, Phoenix, who moderated the session, was asked for comment. “I think the idea of potentially identifying people that have more genetic susceptibility to injuries is very intriguing, because post-traumatic headache and symptoms is always a difficult area to treat, potentially identifying those that with more genetic susceptibility might be helpful. It may also potentially allow us to target specific treatments, especially in this case, looking at different ion channels. There are medications that may work better at ion channel targets than other targets,” said Dr. Green.

He also endorsed the potential value of screening. “Speaking as a parent, I might like to know my child is at higher risk if they’re going to participate in contact sports or other high risk activities,” he said.

Dr. Griffiths and Dr. Green have no relevant financial disclosures.